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Wang Y, Tu M, Gao H, Deng S. Impacts of Circular RNAs on the Osteogenic Differentiation of Dental Stem Cells. Stem Cells Int 2025; 2025:8338337. [PMID: 40376229 PMCID: PMC12081154 DOI: 10.1155/sci/8338337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 04/11/2025] [Indexed: 05/18/2025] Open
Abstract
Dental stem cells are widely viewed as good options for bone regeneration because of their ease of acquisition, innate ability to renew themselves, and ability to differentiate into different types of cells. However, the process of osteogenic differentiation of dental stem cells is orchestrated by an intricate system of regulatory mechanisms. Recent studies have demonstrated the critical impacts of circular RNAs (circRNAs) on osteogenic differentiation of dental stem cells. Exploring the roles and regulatory pathways of circRNAs in dental stem cells could identify novel targets and approaches for utilizing dental stem cell therapy in clinical settings. This review provides a comprehensive overview of the functions and mechanisms of circRNAs, with a particular focus on their expression patterns and regulatory roles in osteogenic differentiation of various dental stem cell types. Furthermore, this review discusses current research challenges in this field and proposes future directions for advancing our understanding of circRNA-mediated regulation in dental stem cell biology.
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Affiliation(s)
- Yang Wang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China
| | - Meijie Tu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China
| | - Huihui Gao
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China
| | - Shuli Deng
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China
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Suwittayarak R, Klincumhom N, Phrueksotsai C, Limjeerajarus N, Limjeerajarus CN, Egusa H, Osathanon T. Shear stress preconditioning enhances periodontal ligament stem cell survival. Arch Oral Biol 2025; 173:106232. [PMID: 40086040 DOI: 10.1016/j.archoralbio.2025.106232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/07/2025] [Accepted: 03/10/2025] [Indexed: 03/16/2025]
Abstract
OBJECTIVE The study investigated in vitro the influences of shear stress preconditioning on human periodontal ligament stem cells (hPDLSCs) under serum deprivation. DESIGN hPDLSCs were subjected to shear stress at 0.5 and 5 dyn/cm², both with and without serum starvation. Cell viability and apoptosis were assessed using the Resazurin assay and flow cytometry analysis, respectively. Gene and protein expressions were analysed by real-time polymerase chain reaction, immunofluorescent staining, and Western blotting. RESULTS Our results revealed that shear stress potentially mitigated serum derivation-induced cell death by inducing cell viability, enhancing colony formation, and inhibiting cell apoptosis. The addition of an ERK inhibitor inhibited the shear stress-induced cell apoptosis resistance. Shear stress treatment upregulated cell viability-related gene expression, including SOX2, SOD1 and BIRC5. In particular, shear stress promoted the nuclear translocation of SOX2. Meanwhile, the expression of BIRC5 was not inhibited by cycloheximide. Shear stress-induced SOX2 and BIRC5 expression was attenuated by PI3K and ERK inhibitors, respectively. CONCLUSIONS Shear stress contributes to promoting SOX2 and BIRC5 expression by hPDLSCs, implicating the promotion of stemness and cell survival under serum starvation.
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Affiliation(s)
- Ravipha Suwittayarak
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand
| | - Nuttha Klincumhom
- Center of Excellence for Regenerative Dentistry and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand
| | - Chaloemrit Phrueksotsai
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand
| | - Nuttapol Limjeerajarus
- Office of Academic Affairs, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand
| | - Chalida Nakalekha Limjeerajarus
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand; Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand
| | - Hiroshi Egusa
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
| | - Thanaphum Osathanon
- Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
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Demirhan HK, Omer Oglou E, Aksoy ZB, Kiran F. Evaluation of the anti-inflammatory, antioxidant and regenerative effects of microbiota-derived postbiotics in human periodontal ligament mesenchymal stromal cells. Clin Oral Investig 2025; 29:262. [PMID: 40263129 PMCID: PMC12014813 DOI: 10.1007/s00784-025-06341-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 04/14/2025] [Indexed: 04/24/2025]
Abstract
OBJECTIVE This study investigates the regenerative and protective effects of postbiotics (cell-free supernatant) derived from the Lactiplantibacillus plantarum EIR/IF-1 strain on human periodontal ligament mesenchymal stromal cells (hPDL-MSCs). MATERIALS AND METHODS hPDL-MSCs were isolated from periodontal ligament tissues (PDL) of wisdom teeth using enzymatic digestion and subsequently characterized through immunophenotyping. The effect of postbiotics on the viability of hPDL-MSCs was assessed using the MTT assay and flow cytometry, while their impact on cell migration was evaluated via the scratch assay. Anti-inflammatory effects of postbiotics were investigated on lipopolysaccharide (LPS, derived from Porphyromonas gingivalis)-stimulated hPDL-MSCs through Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, the antioxidant effects of postbiotics were analyzed in hydrogen peroxide (H₂O₂)-induced hPDL-MSCs by measuring reactive oxygen species (ROS) levels using flow cytometry. The expression of collagen type I (COL1A1) gene was further assessed by quantitative reverse transcription PCR and immunofluorescence staining. RESULTS Treatment with postbiotics (250 µg/mL) significantly increased the viability and migration capability of hPDL-MSCs, while enhancing collagen production for PDL repair. Treatment with postbiotics for 24 h resulted in a 54.53 ± 2.01% reduction in intracellular ROS levels compared to untreated H2O2-induced hPDL-MSCs. Furthermore, postbiotics significantly decreased the production of pro-inflammatory cytokines (IL-8, IL-6, and IL-1β), and increased the anti-inflammatory cytokine IL-10 (2.67-fold) compared to untreated LPS-stimulated hPDL-MSCs. CONCLUSION Our findings indicate that postbiotics exhibit biological activity throughout all stages of the healing process, beginning with the modulation of the inflammatory response to LPS stimulation, followed by the promotion of cell migration, proliferation, and collagen synthesis. Given the unmet need for safe and adjuvant therapeutic approaches that promote comprehensive periodontal regeneration in periodontal diseases, this study presents postbiotics as a promising candidate. CLINICAL RELEVANCE Postbiotics could be integrated into regenerative therapies as a novel bioactive material to improve the healing and regenerative outcomes in periodontal defects by both controlling inflammation and stimulating tissue repair processes.
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Affiliation(s)
- Hazal Kibar Demirhan
- Pharmabiotic Technologies Research Laboratory, Department of Biology, Faculty of Science, Ankara University, Ankara, 06100, Turkey
- Graduate School of Natural and Applied Sciences, Ankara University, Ankara, 06110, Turkey
| | - Emine Omer Oglou
- Pharmabiotic Technologies Research Laboratory, Department of Biology, Faculty of Science, Ankara University, Ankara, 06100, Turkey
- Graduate School of Natural and Applied Sciences, Ankara University, Ankara, 06110, Turkey
| | | | - Fadime Kiran
- Pharmabiotic Technologies Research Laboratory, Department of Biology, Faculty of Science, Ankara University, Ankara, 06100, Turkey.
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Duarte ND, Frigério PB, Chica GEA, Okamoto R, Buchaim RL, Buchaim DV, Messora MR, Issa JPM. Biomaterials for Guided Tissue Regeneration and Guided Bone Regeneration: A Review. Dent J (Basel) 2025; 13:179. [PMID: 40277509 PMCID: PMC12026320 DOI: 10.3390/dj13040179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 04/09/2025] [Accepted: 04/17/2025] [Indexed: 04/26/2025] Open
Abstract
This review aims to provide an overview of the types of membranes, bone substitutes, and mucosal substitutes used for GTR and GBR and briefly explores recent innovations for tissue regeneration and their future perspectives. Since this is a narrative review, no systematic search, meta-analysis, or statistical analysis was conducted. Using biomaterials for GTR and GBR provides a reduction in postoperative morbidity, as it contributes to less invasive clinical procedures, serving as an alternative to autogenous grafts. Moreover, randomized clinical trials (RCTs) and systematic reviews are essential for the evaluation of new biomaterials. These studies provide more robust evidence and help guide clinical practice in the selection of safer and more effective biomaterials, allowing for the personalization of treatment protocols for each patient.
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Affiliation(s)
- Nathália Dantas Duarte
- Department of Diagnosis and Surgery, Araçatuba School of Dentistry (FOA-UNESP), São Paulo State University, Araçatuba 16015-050, Brazil; (N.D.D.); (P.B.F.)
| | - Paula Buzo Frigério
- Department of Diagnosis and Surgery, Araçatuba School of Dentistry (FOA-UNESP), São Paulo State University, Araçatuba 16015-050, Brazil; (N.D.D.); (P.B.F.)
| | - Gloria Estefania Amaya Chica
- Department of Oral and Maxillofacial Surgery and Periodontology, Ribeirão Preto School of Dentistry (FORP-USP), University of São Paulo, Ribeirão Preto 14090-904, Brazil; (G.E.A.C.); (M.R.M.)
| | - Roberta Okamoto
- Department of Basic Sciences, Araçatuba School of Dentistry (FOA-UNESP), São Paulo State University, Araçatuba 16015-050, Brazil;
| | - Rogério Leone Buchaim
- Department of Biological Sciences, Bauru School of Dentistry (FOB-USP), University of São Paulo, Bauru 17012-901, Brazil;
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil;
| | - Daniela Vieira Buchaim
- Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of São Paulo (FMVZ/USP), São Paulo 05508-270, Brazil;
- Anatomy Department, Medical School, University Center of Adamantina (FAI), Adamantina 17800-000, Brazil
- Postgraduate Department, Dentistry School, Faculty of the Midwest Paulista (FACOP), Piratininga 17499-010, Brazil
| | - Michel Reis Messora
- Department of Oral and Maxillofacial Surgery and Periodontology, Ribeirão Preto School of Dentistry (FORP-USP), University of São Paulo, Ribeirão Preto 14090-904, Brazil; (G.E.A.C.); (M.R.M.)
| | - João Paulo Mardegan Issa
- Department of Basic and Oral Biology, Ribeirão Preto School of Dentistry (FORP-USP), University of São Paulo, Ribeirão Preto 14040-904, Brazil
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Miłek O, Schwarz K, Miletić A, Reisinger J, Kovar A, Behm C, Andrukhov O. Regulation and functional importance of human periodontal ligament mesenchymal stromal cells with various rates of CD146+ cells. Front Cell Dev Biol 2025; 13:1532898. [PMID: 40123853 PMCID: PMC11925893 DOI: 10.3389/fcell.2025.1532898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 02/17/2025] [Indexed: 03/25/2025] Open
Abstract
Introduction Mesenchymal stromal cells (MSCs) with high expression of CD146 have superior properties for tissue regeneration. However, high variability in the rate of CD146+ cells among donors is observed. In this study, the possible reasons behind this variability in human periodontal ligament MSCs (hPDL-MSCs) were explored. Methods hPDL-MSCs were isolated from 22 different donors, and rates of CD146+ cells were analyzed by flow cytometry. Furthermore, populations with various rates of CD146+ cells were isolated with magnetic separation. The dependency of cell proliferation, viability, cell cycle, and osteogenic differentiation on the rates of CD146+ cells was investigated. Besides, the effects of various factors, like cell density, confluence, and inflammatory environment on the CD146+ rate and expression were analyzed. Results The rate of CD146+ cells exhibited high variability between donors, with the percentage of CD146+ cells ranging from 3% to 67%. Higher percentage of CD146+ cells was associated with higher proliferation, presumably due to the higher percentage of cells in the S-phase, and higher osteogenic differentiation potential. Prolonged cell confluence and higher cell seeding density led to the decline in the rate of CD146+ cells. The surface rate of CD146 in hPDL-MSCs was stimulated by the treatment with interleukin-1β and tumor necrosis factor-α, and inhibited by the treatment with interferon-γ. Conclusion These results suggest that hPDL-MSCs with high rate of CD146+ cells are a promising subpopulation for enhancing the effectiveness of MSC-based regenerative therapies, however the rate of CD146 is affected by various factors, which must be considered for cell propagation and their potential application in vivo.
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Affiliation(s)
| | | | | | | | | | | | - Oleh Andrukhov
- Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
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Xiang M, Zhang G, Liu Y, Liao C, Xiao L, Xiang M, Guan X, Liu J. Polydopamine-functionalized nanohydroxyapatite coated exosomes with enhanced cytocompatibility and osteogenesis for bone regeneration. Biomed Mater Eng 2025; 36:98-109. [PMID: 39973215 DOI: 10.1177/09592989241301662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
BackgroundMesenchymal stem cells-derived exosomes, crucial in regenerative medicine, have been explored for their potential for the functional modification of bone scaffolds.ObjectiveTo design a functionally modified biomimetic nanohydroxyapatite using exosomes and explore its effects on bone regeneration.MethodsA biomimetic nanohydroxyapatite (named as tHA) was fabricated as previous methods using a polydopamine (pDA) structure as a template, and exosomes (Exo) derived from periodontal ligament stem cells (PDLSCs) were used to functionally modify the tHA scaffold material through pDA. The effects of functional composite scaffold (tHA-Exo) on cells proliferation and osteogenic differentiation were investigated. Furthermore, their effect on bone regeneration was also evaluated in vivo.ResultsExosomes can be loaded onto the tHA via pDA and the tHA-Exo releases exosomes in a sustained and stable manner. tHA-Exo showed improved cytocompatibility compared to controls. Additionally, tHA-Exo significantly enhanced the proliferation and osteogenic differentiation of PDLSCs. More importantly, animal experiments have shown that tHA-Exo could dramatically promote bone regeneration.ConclusionThe tHA nanoparticles, functionally modified by the PDLSCs-Exo through pDA, significantly promoted bone regeneration by improving its cytocompatibility and osteogenic potential, which could serve as a promising material for promoting bone regeneration.
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Affiliation(s)
- Mingli Xiang
- Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China
- GuiZhou University Medical College, Guiyang, China
| | - Gengchao Zhang
- Oral Disease Research Key Laboratory of Guizhou Tertiary Institution, School of Stomatology, Zunyi Medical University, Zunyi, China
| | - Yulin Liu
- Oral Disease Research Key Laboratory of Guizhou Tertiary Institution, School of Stomatology, Zunyi Medical University, Zunyi, China
| | - Chengcheng Liao
- Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China
| | - Linlin Xiao
- Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China
| | - Meiling Xiang
- Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China
| | - Xiaoyan Guan
- Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China
| | - Jianguo Liu
- GuiZhou University Medical College, Guiyang, China
- Oral Disease Research Key Laboratory of Guizhou Tertiary Institution, School of Stomatology, Zunyi Medical University, Zunyi, China
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Jia L, Xiao H, Hao Z, Sun S, Zhao W, Gong Z, Gu W, Wen Y. Senolytic elimination of senescent cells improved periodontal ligament stem cell-based bone regeneration partially through inhibiting YAP. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2025; 1872:119921. [PMID: 39971252 DOI: 10.1016/j.bbamcr.2025.119921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 01/28/2025] [Accepted: 02/13/2025] [Indexed: 02/21/2025]
Abstract
Periodontal ligament stem cell (PDLSC)-based tissue engineering is an important method to promote periodontal tissue regeneration. However, PDLSCs are susceptible to the effects of replicative senescence, leading to reduced proliferation and differentiation abilities and weakened tissue regeneration potential. Senolytics (the combination of dasatinib and quercetin) are drugs that inhibit cellular aging through inducing the apoptosis of senescent cells, but whether they have positive effects during the senescence of PDLSCs is unknown. The present study established a long-term in vitro culture model of PDLSCs and then analyzed the effects of senolytics on the senescence, apoptosis, and osteogenic differentiation of PDLSCs in vitro and PDLSC-based tissue regeneration in vivo. The results showed that senolytics delayed the process of aging in prolonged-cultured PDLSCs and promoted the elimination and apoptosis of senescent cells. Moreover, senolytics improved the osteogenic differentiation ability of both young and senescent PDLSCs in vitro and promoted PDLSC-based alveolar bone regeneration in vivo. Furthermore, senolytics inhibited the expression of YAP in senescent PDLSCs. Their antiaging effects were enhanced when combined with the YAP inhibitor verteporfin, but were inhibited when combined with the YAP activator NIBR-LTSi. Taken together, these findings suggest that senolytics promoted the elimination of senescent PDLSCs and enhanced senescent PDLSC-based bone regeneration, partially through the inhibition of YAP expression.
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Affiliation(s)
- Linglu Jia
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Han Xiao
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Zhenghao Hao
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Shaoqing Sun
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Wenxi Zhao
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Zikai Gong
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Weiting Gu
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, China.
| | - Yong Wen
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China; Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China.
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Wang Y, Zhang FQ, Fan ZP, Zhu XL, Yan WH, Zhang XL. WDR36 inhibits the osteogenic differentiation and migration of periodontal ligament stem cells. World J Stem Cells 2025; 17:99132. [PMID: 40061266 PMCID: PMC11885943 DOI: 10.4252/wjsc.v17.i2.99132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 11/23/2024] [Accepted: 01/16/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Periodontitis is an inflammatory disease caused by the host's immune response and various interactions between pathogens, which lead to the loss of connective tissue and bone. In recent years, mesenchymal stem cell (SC) transplantation technology has become a research hotspot, which can form periodontal ligament, cementum, and alveolar bone through proliferation and differentiation. AIM To elucidate the regulatory effects of WD repeat-containing protein 36 (WDR36) on the senescence, migration, and osteogenic differentiation of periodontal ligament SCs (PDLSCs). METHODS The migration and chemotaxis of PDLSCs were detected by the scratch-wound migration test and transwell chemotaxis test. Alkaline phosphatase (ALP) activity, Alizarin red staining, calcium content, and real-time reverse transcription polymerase chain reaction (RT-qPCR) of key transcription factors were used to detect the osteogenic differentiation function of PDLSCs. Cell senescence was determined by senescence-associated β-galactosidase staining. RESULTS The 24-hour and 48-hour scratch-wound migration test and 48-hour transwell chemotaxis test showed that overexpression of WDR36 inhibited the migration/chemotaxis of PDLSCs. Simultaneously, WDR36 depletion promoted the migration/chemotaxis of PDLSCs. The results of ALP activity, Alizarin red staining, calcium content, and RT-qPCR showed that overexpression of WDR36 inhibited the osteogenic differentiation of PDLSCs, and WDR36 depletion promoted the osteogenic differentiation of PDLSCs. Senescence-associated β-galactosidase staining showed that 0.1 μg/mL icariin (ICA) and overexpression of WDR36 inhibited the senescence of PDLSCs, and WDR36 depletion promoted the osteogenic differentiation of PDLSCs. CONCLUSION WDR36 inhibits the migration and chemotaxis, osteogenic differentiation, and senescence of PDLSCs; 0.1 μg/mL ICA inhibits the senescence of PDLSCs. Therefore, WDR36 might serve as a target for periodontal tissue regeneration and the treatment of periodontitis.
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Affiliation(s)
- Yi Wang
- Department of Wangfujing General School of Stomatology, Capital Medical University, Beijing 100070, China
| | - Feng-Qiu Zhang
- Department of Periodontics School of Stomatology, Capital Medical University, Beijing 100070, China.
| | - Zhi-Peng Fan
- Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Beijing 100070, China
- Beijing Laboratory of Oral Health, Capital Medical University, Beijing 100070, China
- Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing 100070, China
| | - Xin-Ling Zhu
- Department of Periodontology, Hangzhou Stomatology Hospital, Hangzhou 310006, Zhejiang Province, China
| | - Wan-Hao Yan
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100070, China
| | - Xiu-Li Zhang
- Department of Stomatology, Civil Aviation General Hospital, Beijing 100123, China
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Lyu P, Liu J, Ouyang X, Wang Y, Liu W, Zhong J. Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing protein 5 affects the progression of periodontitis by regulating the function of periodontal membrane cells. J Dent Sci 2025; 20:325-334. [PMID: 39873066 PMCID: PMC11762624 DOI: 10.1016/j.jds.2024.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 07/08/2024] [Indexed: 01/30/2025] Open
Abstract
Background/purpose Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing protein 5 (NLRC5) plays a regulatory role in innate and adaptive immunity. However, its role in periodontitis remains unclear. This study investigated the effects of NLRC5 on periodontitis and the underlying mechanism. Materials and methods Experimental periodontitis models of wild-type and Nlrc5 knockout mice were established to detect alveolar bone loss. The inflammatory environment was established with Porphyromonas. gingivalis lipopolysaccharide (P. gingivalis LPS). The expression of NLRC5 in periodontal ligament stem cells (PDLSCs) were detected with P. gingivalis LPS stimulated. After knocking-down or overexpressing the NLRC5 expression level, the inflammatory cytokine level and osteogenic ability of PDLSCs were detected. Results The Nlrc5 knockout mice exhibited greater alveolar bone loss in periodontitis. In the presence of P. gingivalis LPS, the expression of NLRC5 decreased. Downregulating NLRC5 increased the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α). Upregulated NLRC5 inhibited nuclear factor kappa-B (NF-κB) signaling and inhibited the expression of those proinflammatory factors. NLRC5 had a positive regulatory effect on the osteogenic differentiation of PDLSCs. When NLRC5 was knocked down, the ALP activity and the number of mineralized nodules in PDLSCs decreased. Conversely, overexpression of NLRC5 enhanced the osteogenic differentiation ability of PDLSCs. Overexpression of NLRC5 increased the osteogenic differentiation of PDLSCs in inflammatory environments. Conclusion NLRC5 affects the progression of periodontitis by regulating the function of PDLSCs. NLRC5 reduced the expression of inflammatory factors by inhibiting NF-κB, and had a positive regulatory effect on the osteogenic differentiation of PDLSCs.
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Affiliation(s)
- Peiying Lyu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Jianru Liu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Xiangying Ouyang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Yuanbo Wang
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Wenyi Liu
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
| | - Jinsheng Zhong
- Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China
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Guo J, Jia H. DNMT3A transcriptionally downregulated by KLF5 alleviates LPS-induced inflammatory response and promotes osteogenic differentiation in hPDLSCs. J Appl Oral Sci 2024; 32:e20240268. [PMID: 39476105 DOI: 10.1590/1678-7757-2024-0268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 09/10/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Periodontitis is an inflammatory disease typically characterized by the destruction of periodontal tissues and complicated etiology. DNA methyltransferase 3A (DNMT3A) has been implicated in possessing pro-inflammatory properties. This study sought to explore the role of DNMT3A in periodontitis and its relevant mechanism. METHODOLOGY Lipopolysaccharide (LPS) was used to induce inflammation in human periodontal ligament stem cells (hPDLSCs). DNMT3A and KLF5 expressions were detected using RT-qPCR and western blot. The levels of inflammatory cytokines and inflammation-related proteins were detected using ELISA and western blot. NF-κB p65 expression was detected using immunofluorescence (IF) assay, while osteogenic differentiation was assessed using ALP assay and ARS staining. Western blot was used to measure the protein contents associated with osteogenic differentiation. DNMT3A activity was detected using luciferase report assay and chromatin immunoprecipitation (ChIP) was used to verify the interaction between KLF5 and DNMT3A. RESULTS DNMT3A expression increased in LPS-induced hPDLSCs. Silencing DNMT3A suppressed the LPS-induced inflammation in hPDLSCs, while promoting osteogenic differentiation. It was also found that transcriptional factor KLF5 could bind to DNMT3A promoters and regulate DNMT3A expression. Rescue experiments showed that KLF5 interference partially counteracted the inhibitory impacts of DNMT3A deficiency on inflammation and the promotive effects on osteogenic differentiation in LPS-induced hPDLSCs. CONCLUSION DNMT3A, when transcriptionally downregulated by KLF5, could alleviate LPS-challenged inflammatory responses and facilitate osteogenic differentiation in hPDLSCs.
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Affiliation(s)
- Jianling Guo
- Suzhou Stomatology Hospital (Group) Co. Ltd. Suzhou, Department of Pediatric Dentistry, Jiangsu, China
| | - Huijie Jia
- Minhang Hospital, Fudan University, Department of Stomatology, Shanghai, China
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Inchingolo AM, Inchingolo AD, Nardelli P, Latini G, Trilli I, Ferrante L, Malcangi G, Palermo A, Inchingolo F, Dipalma G. Stem Cells: Present Understanding and Prospects for Regenerative Dentistry. J Funct Biomater 2024; 15:308. [PMID: 39452606 PMCID: PMC11508604 DOI: 10.3390/jfb15100308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 10/02/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024] Open
Abstract
Regenerative medicine in dentistry focuses on repairing damaged oral tissues using advanced tools like stem cells, biomaterials, and tissue engineering (TE). Mesenchymal stem cells (MSCs) from dental sources, such as dental pulp and periodontal ligament, show significant potential for tissue regeneration due to their proliferative and differentiative abilities. This systematic review, following PRISMA guidelines, evaluated fifteen studies and identified effective strategies for improving dental, periodontal, and bone tissue regeneration through scaffolds, secretomes, and bioengineering methods. Key advancements include the use of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) to boost cell viability and manage inflammation. Additionally, pharmacological agents like matrine and surface modifications on biomaterials improve stem cell adhesion and promote osteogenic differentiation. By integrating these approaches, regenerative medicine and TE can optimize dental therapies and enhance patient outcomes. This review highlights the potential and challenges in this field, providing a critical assessment of current research and future directions.
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Affiliation(s)
- Angelo Michele Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Alessio Danilo Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Paola Nardelli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Giulia Latini
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Irma Trilli
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Laura Ferrante
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Giuseppina Malcangi
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Andrea Palermo
- College of Medicine and Dentistry, Birmingham B4 6BN, UK;
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
| | - Gianna Dipalma
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (A.M.I.); (A.D.I.); (P.N.); (G.L.); (I.T.); (L.F.); (G.D.)
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Li Z, Li J, Dai S, Liu R, Guo Q, Liu F. Research Status and Trends in Periodontal Ligament Stem Cells: A Bibliometric Analysis over the Past Two Decades. Stem Cells Int 2024; 2024:9955136. [PMID: 39372680 PMCID: PMC11452234 DOI: 10.1155/2024/9955136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 08/21/2024] [Accepted: 08/31/2024] [Indexed: 10/08/2024] Open
Abstract
Objective Currently, the summaries of research on periodontal ligament stem cells (PDLSCs) are mainly reviews, and the systematic evaluation of all relevant studies is lacking. The aim of our study was to reveal the research status and developmental trends of PDLSCs using bibliometric analyses. Methods Publications on PDLSC from 2004 to 2023 in the PubMed database were searched and then screened according to certain inclusion and exclusion criteria. Two researchers browsed the included papers and recorded information such as the research type and research model. The VOSviewer software was used to analyze the distribution of authors, journals, and institutions. The contents and directions of PDLSC research were summarized by analyzing high-frequency keywords. The CiteSpace software was used to monitor burst words, determine hot factors, and indicate developmental trends. Results During the past two decades, the number of studies on PDLSCs increased. China published the most related papers. The primary type of article was basic research. Among core journals, the Journal of Periodontal Research had the highest number of publications. The Fourth Military Medical University (China) was leading in the number of articles on PDLSCs. Research topics mainly included mechanism of periodontal diseases, tissue engineering and regeneration, biological characteristics of PDLSCs, and comparison with other stem cells. Infectious inflammation and mechanical stimulation were important pathological conditions and research topics. Conclusion The research of PDLSCs is still in a rapid development stage. Our study provides new insights into the current research status and future trend in this field.
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Affiliation(s)
- Zhengyang Li
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Jinyi Li
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Shanshan Dai
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Ruirui Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of ProsthodonticsCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Qingyu Guo
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
| | - Fei Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
- Department of Pediatric DentistryCollege of StomatologyXi'an Jiaotong University, Xi'an 710004, China
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Kim E, Park Y, Yun M, Kim B. Functions of Hemp-Induced Exosomes against Periodontal Deterioration Caused by Fine Dust. Int J Mol Sci 2024; 25:10331. [PMID: 39408660 PMCID: PMC11477052 DOI: 10.3390/ijms251910331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 09/23/2024] [Accepted: 09/24/2024] [Indexed: 10/19/2024] Open
Abstract
Although fine dust is linked to numerous health issues, including cardiovascular, neurological, respiratory, and cancerous diseases, research on its effects on oral health remains limited. In this study, we investigated the protective effects of mature hemp stem extract-induced exosomes (MSEIEs) on periodontal cells exposed to fine dust. Using various methods, including microRNA profiling, PCR, flow cytometry, immunocytochemistry, ELISA, and Alizarin O staining, we found that MSE treatment upregulated key microRNAs, such as hsa-miR-122-5p, hsa-miR-1301-3p, and hsa-let-7e-5p, associated with vital biological functions. MSEIEs exhibited three primary protective functions: suppressing inflammatory genes while activating anti-inflammatory ones, promoting the differentiation of periodontal ligament stem cells (PDLSCs) into osteoblasts and other cells, and regulating LL-37 and MCP-1 expression. These findings suggest that MSEIEs have potential as functional biomaterials for applications in pharmaceuticals, cosmetics, and food industries.
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Affiliation(s)
- Eunhee Kim
- Department of Food Science and Biotechnology, Andong National University, Andong 36729, Republic of Korea;
| | - Yoonjin Park
- Department of Bio-Hemp Technology, Andong Science College, Andong 36616, Republic of Korea;
| | - Mihae Yun
- Department of Dental Hygiene, Andong Science College, Andong 36616, Republic of Korea
| | - Boyong Kim
- EVERBIO, 131, Jukhyeon-gil, Gwanghyewon-myeon, Jincheon-gun 27809, Republic of Korea
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14
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Rofaani E, Mardani MW, Yutiana PN, Amanda O, Darmawan N. Differentiation of mesenchymal stem cells into vascular endothelial cells in 3D culture: a mini review. Mol Biol Rep 2024; 51:781. [PMID: 38913199 DOI: 10.1007/s11033-024-09743-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 06/20/2024] [Indexed: 06/25/2024]
Abstract
Mesenchymal Stem Cells, mesodermal origin and multipotent stem cells, have ability to differentiate into vascular endothelial cells. The cells are squamous in morphology, inlining, and protecting blood vessel tissue, as well as maintaining homeostatic conditions. ECs are essential in vascularization and blood vessels formation. The differentiation process, generally carried out in 2D culture systems, were relied on growth factors induction. Therefore, an artificial extracellular matrix with relevant mechanical properties is essential to build 3D culture models. Various 3D fabrication techniques, such as hydrogel-based and fibrous scaffolds, scaffold-free, and co-culture to endothelial cells were reviewed and summarized to gain insights. The obtained MSCs-derived ECs are shown by the expression of endothelial gene markers and tubule-like structure. In order to mimicking relevant vascular tissue, 3D-bioprinting facilitates to form more complex microstructures. In addition, a microfluidic chip with adequate flow rate allows medium perfusion, providing mechanical cues like shear stress to the artificial vascular vessels.
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Affiliation(s)
- E Rofaani
- Group Research of Theranostics, Research Center for Vaccine and Drug, Research Organization of Health, National Research and Innovation Agency, LAPTIAB Building No 611 PUSPIPTEK or KST BJ Habibie, Tangerang Selatan, Banten, 15315, Indonesia.
| | - M W Mardani
- Department of Biology, Faculty of Mathematics and Natural Sciences, Sebelas Maret University, Ir. Sutami Street No. 36A, Jebres District, Surakarta, Central Java, 57126, Indonesia
| | - P N Yutiana
- Department of Biology, Faculty of Mathematics and Natural Sciences, Sebelas Maret University, Ir. Sutami Street No. 36A, Jebres District, Surakarta, Central Java, 57126, Indonesia
| | - O Amanda
- Department of Technique of Biomedis, Faculty of Technique of Industry, Institut Teknologi Sumatera, Jalan Terusan Ryacudu, Way Huwi, Jati Agung, Lampung Selatan, Lampung, 35365, Indonesia
| | - N Darmawan
- Laboratory of Inorganic Chemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University, Kampus IPB Dramaga, Bogor, West Java, 16880, Indonesia
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Wang D, Guo Y, Heng BC, Zhang X, Wei Y, He Y, Xu M, Xia B, Deng X. Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration. Bone Res 2024; 12:23. [PMID: 38594236 PMCID: PMC11003965 DOI: 10.1038/s41413-024-00325-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 02/04/2024] [Accepted: 03/08/2024] [Indexed: 04/11/2024] Open
Abstract
Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.
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Affiliation(s)
- Dandan Wang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yaru Guo
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, P. R. China
| | - Boon Chin Heng
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, P. R. China
| | - Xuehui Zhang
- Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, P. R. China
| | - Yan Wei
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, P. R. China
| | - Ying He
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, P. R. China
| | - Mingming Xu
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, P. R. China
| | - Bin Xia
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
| | - Xuliang Deng
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, P. R. China.
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16
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Suciu TS, Feștilă D, Berindan-Neagoe I, Nutu A, Armencea G, Aghiorghiesei AI, Vulcan T, Băciuț M. Circular RNA-Mediated Regulation of Oral Tissue-Derived Stem Cell Differentiation: Implications for Oral Medicine and Orthodontic Applications. Stem Cell Rev Rep 2024; 20:656-671. [PMID: 38279054 PMCID: PMC10984898 DOI: 10.1007/s12015-024-10683-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 01/28/2024]
Abstract
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs (ncRNAs) which unlike linear RNAs, have a covalently closed continuous loop structure. circRNAs are found abundantly in human cells and their biology is complex. They feature unique expression to different types of cells, tissues, and developmental stages. To the present, the functional roles of circular RNAs are not fully understood. They reportedly act as microRNA (miRNA) sponges, therefore having key regulatory functions in diverse physiological and pathological processes. As for dentistry field, lines of evidence indicate that circRNAs play vital roles in the odontogenic and osteogenic differentiation of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). Abnormal expression of circRNAs have been found in other areas of pathology frequently reflected also in the oral environment, such as inflammation or bone and soft tissue loss. Therefore, circRNAs could be of significant importance in various fields in dentistry, especially in bone and soft tissue engineering and regeneration. Understanding the molecular mechanisms occurring during the regulation of oral biological and tissue remodeling processes could augment the discovery of novel diagnostic biomarkers and therapeutic strategies that will improve orthodontic and other oral therapeutic protocols.
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Affiliation(s)
- Tudor-Sergiu Suciu
- Department of Orthodontics and Dentofacial Orthopedics, Iuliu Hațieganu University of Medicine and Pharmacy, 400083, Cluj-Napoca, Romania
| | - Dana Feștilă
- Department of Orthodontics and Dentofacial Orthopedics, Iuliu Hațieganu University of Medicine and Pharmacy, 400083, Cluj-Napoca, Romania.
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400337, Cluj-Napoca, Romania
| | - Andreea Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400337, Cluj-Napoca, Romania
| | - Gabriel Armencea
- Department of Maxillofacial Surgery and Implantology, Iuliu Hațieganu University of Medicine and Pharmacy, 400029, Cluj-Napoca, Romania
| | - Alexandra Iulia Aghiorghiesei
- Department of Prosthodontics and Dental Materials, Iuliu Hațieganu University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania
| | - Talida Vulcan
- Department of Dermatology, Iuliu Hațieganu University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania
| | - Mihaela Băciuț
- Department of Maxillofacial Surgery and Implantology, Iuliu Hațieganu University of Medicine and Pharmacy, 400029, Cluj-Napoca, Romania
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Wang J, Zhao Z, Yang K, Bai Y. Research progress in cell therapy for oral diseases: focus on cell sources and strategies to optimize cell function. Front Bioeng Biotechnol 2024; 12:1340728. [PMID: 38515628 PMCID: PMC10955105 DOI: 10.3389/fbioe.2024.1340728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 02/23/2024] [Indexed: 03/23/2024] Open
Abstract
In recent years, cell therapy has come to play an important therapeutic role in oral diseases. This paper reviews the active role of mesenchymal stem cells, immune cell sources, and other cells in oral disorders, and presents data supporting the role of cell therapy in oral disorders, including bone and tooth regeneration, oral mucosal disorders, oral soft tissue defects, salivary gland dysfunction, and orthodontic tooth movement. The paper will first review the progress of cell optimization strategies for oral diseases, including the use of hormones in combination with stem cells, gene-modified regulatory cells, epigenetic regulation of cells, drug regulation of cells, cell sheets/aggregates, cell-binding scaffold materials and hydrogels, nanotechnology, and 3D bioprinting of cells. In summary, we will focus on the therapeutic exploration of these different cell sources in oral diseases and the active application of the latest cell optimization strategies.
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Affiliation(s)
| | | | | | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
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Yang SY, Hu Y, Zhao R, Zhou YN, Zhuang Y, Zhu Y, Ge XL, Lu TW, Lin KL, Xu YJ. Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway. J Nanobiotechnology 2024; 22:94. [PMID: 38449005 PMCID: PMC10918894 DOI: 10.1186/s12951-024-02352-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 02/20/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.
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Affiliation(s)
- Shi-Yuan Yang
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
| | - Yue Hu
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
| | - Ran Zhao
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
- Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-Ning Zhou
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
| | - Yu Zhuang
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Zhu
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
| | - Xiao-Li Ge
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
- Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting-Wei Lu
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kai-Li Lin
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China.
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Yuan-Jin Xu
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
- College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai, China.
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Wu Y, Wang X, Zhang Y, Wen Z, Li Y, Zhang K, Gosar N, Li Q, Mao J, Gong S. Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation. Int J Mol Sci 2024; 25:2947. [PMID: 38474198 DOI: 10.3390/ijms25052947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/25/2024] [Accepted: 03/01/2024] [Indexed: 03/14/2024] Open
Abstract
Periodontitis is a bacteria-induced inflammatory disease characterized by the progressive destruction of periodontal supporting tissues. Periodontal ligament stem cells (PDLSCs) are capable of differentiating into osteoblasts, which is an important stem cell source for endogenous periodontal tissue regeneration. Lysine lactylation (Kla) is a novel post-translational modification of proteins that is recently thought to be associated with osteogenic differentiation. Here, we found that lactylation levels are reduced both in the periodontal tissue of rats with periodontitis and lipopolysaccharide (LPS)-stimulated human PDLSCs. Proanthocyanidins were able to promote the osteogenesis of inflamed PDLSCs by restoring lactylation levels. Mechanistically, proanthocyanidins increased lactate production and restored the lactylation levels of PDLSCs, which recovered osteogenesis of inflamed PDLSCs via the Wnt/β-catenin pathway. These results provide evidence on how epigenetic regulation by pharmacological agents influence the osteogenic phenotype of stem cells and the process of periodontal tissue repair. Our current study highlights the valuable potential of natural product proanthocyanidins in the regenerative engineering of periodontal tissues.
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Affiliation(s)
- Yaxin Wu
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Xiangyao Wang
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Yuxiao Zhang
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Zhihao Wen
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Yuanyuan Li
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Kehan Zhang
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Nuerlan Gosar
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Qilin Li
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Jing Mao
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
| | - Shiqiang Gong
- Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, China
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20
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Radzki D, Negri A, Kusiak A, Obuchowski M. Matrix Metalloproteinases in the Periodontium-Vital in Tissue Turnover and Unfortunate in Periodontitis. Int J Mol Sci 2024; 25:2763. [PMID: 38474009 DOI: 10.3390/ijms25052763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/24/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
The extracellular matrix (ECM) is a complex non-cellular three-dimensional macromolecular network present within all tissues and organs, forming the foundation on which cells sit, and composed of proteins (such as collagen), glycosaminoglycans, proteoglycans, minerals, and water. The ECM provides a fundamental framework for the cellular constituents of tissue and biochemical support to surrounding cells. The ECM is a highly dynamic structure that is constantly being remodeled. Matrix metalloproteinases (MMPs) are among the most important proteolytic enzymes of the ECM and are capable of degrading all ECM molecules. MMPs play a relevant role in physiological as well as pathological processes; MMPs participate in embryogenesis, morphogenesis, wound healing, and tissue remodeling, and therefore, their impaired activity may result in several problems. MMP activity is also associated with chronic inflammation, tissue breakdown, fibrosis, and cancer invasion and metastasis. The periodontium is a unique anatomical site, composed of a variety of connective tissues, created by the ECM. During periodontitis, a chronic inflammation affecting the periodontium, increased presence and activity of MMPs is observed, resulting in irreversible losses of periodontal tissues. MMP expression and activity may be controlled in various ways, one of which is the inhibition of their activity by an endogenous group of tissue inhibitors of metalloproteinases (TIMPs), as well as reversion-inducing cysteine-rich protein with Kazal motifs (RECK).
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Affiliation(s)
- Dominik Radzki
- Department of Periodontology and Oral Mucosa Diseases, Faculty of Medicine, Medical University of Gdańsk, 80-208 Gdańsk, Poland
- Division of Molecular Bacteriology, Institute of Medical Biotechnology and Experimental Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Alessandro Negri
- Division of Molecular Bacteriology, Institute of Medical Biotechnology and Experimental Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
| | - Aida Kusiak
- Department of Periodontology and Oral Mucosa Diseases, Faculty of Medicine, Medical University of Gdańsk, 80-208 Gdańsk, Poland
| | - Michał Obuchowski
- Division of Molecular Bacteriology, Institute of Medical Biotechnology and Experimental Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
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21
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Wu Y, Gong P. Scopolamine regulates the osteogenic differentiation of human periodontal ligament stem cells through lactylation modification of RUNX2 protein. Pharmacol Res Perspect 2024; 12:e1169. [PMID: 38258916 PMCID: PMC10804664 DOI: 10.1002/prp2.1169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 11/06/2023] [Accepted: 12/03/2023] [Indexed: 01/24/2024] Open
Abstract
Periodontal ligament stem cells (PDLSCs) are important mesenchymal stem cells contributing to regenerating lost periodontal tissues and repairing bone defects. Studies on the molecular mechanism affecting the osteogenic differentiation of PDLSCs are necessary. Scopolamine (SCO) is known as a regulator of neural cell damage. The focus of the current study is on unveiling the role of SCO-mediated molecular mechanism in the osteogenic differentiation of PDLSCs. Through CCK-8 assay and LDH detection, we confirmed that SCO enhanced the viability of PDLSCs. Moreover, we determined that SCO induced the PDLSCs osteogenic differentiation, according to data of ALP activity measurement and ARS staining. Mechanistically, we performed western blot and identified that SCO could promote the lactylation of runt-related transcription factor 2 (RUNX2). We also found through rescue assays that knockdown of RUNX2 could reverse the effect of SCO treatment on the osteogenic differentiation of PDLSCs. Further mechanism investigation revealed that lactylation of RUNX2 at K176 site enhances the protein stability of RUNX2 through deubiquitination. Collectively, our present study unveils that SCO stabilizes RUNX2 to promote the osteogenic differentiation of PDLSCs through the lactylation modification of RUNX2.
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Affiliation(s)
- Ying Wu
- Department of PeriodonticsAffiliated Stomatology Hospital of Guangzhou Medical UniversityGuangzhouChina
- Guangdong Engineering Research Center of Oral Restoration and ReconstructionGuangzhouChina
- Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative MedicineGuangzhouChina
| | - Pan Gong
- Department of StomatologyAffiliated Cancer Hospital & Institute of Guangzhou Medical UniversityGuangzhouChina
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22
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Ponnaiyan D, Rughwani RR, Victor DJ, Shetty G. Stem Cells in the Periodontium-Anatomically Related Yet Physiologically Diverse. Eur J Dent 2024; 18:1-13. [PMID: 36588293 PMCID: PMC10959637 DOI: 10.1055/s-0042-1759487] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Periodontitis is a complex chronic disease discernible by the deterioration of periodontal tissue. The goal of periodontal therapy is to achieve complete tissue regeneration, and one of the most promising treatment options is to harness the regenerative potential of stem cells available within the periodontal complex. Periodontal ligament stem cells, gingival mesenchymal stem cells, oral periosteal stem cells, and dental follicle stem cells have structural similarities, but their immunological responses and features differ. The qualities of diverse periodontal stem cells, their immune-modulatory effects, and variances in their phenotypes and characteristics will be discussed in this review. Although there is evidence on each stem cell population in the periodontium, understanding the differences in markers expressed, the various research conducted so far on their regenerative potential, will help in understanding which stem cell population will be a better candidate for tissue engineering. The possibility of selecting the most amenable stem cell population for optimal periodontal regeneration and the development and current application of superior tissue engineering treatment options such as autologous transplantation, three-dimensional bioengineered scaffolds, dental stem cell-derived extracellular vesicles will be explored.
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Affiliation(s)
- Deepa Ponnaiyan
- Department of Periodontics and Oral Implantology, SRM Dental College and Hospital, Ramapuram, Chennai, Tamil Nadu, India
| | - Roshan R. Rughwani
- Department of Periodontics and Oral Implantology, SRM Dental College and Hospital, Ramapuram, Chennai, Tamil Nadu, India
| | - Dhayanand John Victor
- Department of Periodontics and Oral Implantology, SRM Dental College and Hospital, Ramapuram, Chennai, Tamil Nadu, India
| | - Ganesh Shetty
- Dental and Orthodontic Clinic, Bangalore, Karnataka, India
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23
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Jiang Y, Yang K, Jia B, Gao Y, Chen Y, Chen P, Lu X, Zhang W, Wang X. Nicotine destructs dental stem cell-based periodontal tissue regeneration. J Dent Sci 2024; 19:231-245. [PMID: 38303843 PMCID: PMC10829564 DOI: 10.1016/j.jds.2023.04.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 04/18/2023] [Indexed: 02/03/2024] Open
Abstract
Background/purpose Nicotine is a widely known addictive and toxic substance in cigarette that exacerbates periodontitis. However, its deleterious effects on dental stem cells and subsequent implications in tissue regeneration remain unclear. This study aimed to explore the effects of nicotine on the regenerative capacity of human periodontal ligament stem cells (hPDLSCs) based on transcriptomics and proteomics, and determined possible targeted genes associated with smoking-related periodontitis. Materials and methods hPDLSCs were treated with different concentrations of nicotine ranging from 10-3 to 10-8 M. Transcriptomics and proteomics were performed and confirmed employing Western blot, 5-ethynyl-2'-deoxyuridine (EdU), and alkaline phosphatase (ALP) staining. A ligature-induced periodontitis mouse model was established and administrated with nicotine (16.2 μg/10 μL) via gingival sulcus. The bone resorption was assessed by micro-computed tomography and histological staining. Key genes were identified using multi-omics analysis with verifications in hPDLSCs and human periodontal tissues. Results Based on enrichments analysis, nicotine-treated hPDLSCs exhibited decreased proliferation and differentiation abilities. Local administration of nicotine in mouse model significantly aggravated bone resorption and undermined periodontal tissue regeneration by inhibiting the endogenous dental stem cells regenerative ability. HMGCS1, GPNMB, and CHRNA7 were hub-genes according to the network analysis and corelated with proliferation and differentiation capabilities, which were also verified in both cells and tissues. Conclusion Our study investigated the destructive effects of nicotine on the regeneration of periodontal tissues from aspects of in vitro and in vivo with the supporting information from both transcriptome and proteome, providing novel targets into the molecular mechanisms of smoking-related periodontitis.
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Affiliation(s)
- Yuran Jiang
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Kuan Yang
- School of Stomatology, Qingdao University, Qingdao, Shandong, China
| | - Bo Jia
- State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Forth Military Medical University, Xi'an, Shaanxi, China
| | - Yuan Gao
- State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Forth Military Medical University, Xi'an, Shaanxi, China
- School of Biomedical Science, Li Ka-shing School of Medicine, Hong Kong University, Hong Kong, China
| | - Yujiang Chen
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Peng Chen
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Xiaoxi Lu
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Wei Zhang
- State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Forth Military Medical University, Xi'an, Shaanxi, China
| | - Xiaojing Wang
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
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24
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Santilli F, Fabrizi J, Santacroce C, Caissutti D, Spinello Z, Candelise N, Lancia L, Pulcini F, Delle Monache S, Mattei V. Analogies and Differences Between Dental Stem Cells: Focus on Secretome in Combination with Scaffolds in Neurological Disorders. Stem Cell Rev Rep 2024; 20:159-174. [PMID: 37962698 PMCID: PMC10799818 DOI: 10.1007/s12015-023-10652-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2023] [Indexed: 11/15/2023]
Abstract
Mesenchymal stem cells (MSCs) are well known for their beneficial effects, differentiation capacity and regenerative potential. Dental-derived MSCs (DSCs) are more easily accessible and have a non-invasive isolation method rather than MSCs isolated from other sources (umbilical cord, bone marrow, and adipose tissue). In addition, DSCs appear to have a relevant neuro-regenerative potential due to their neural crest origin. However, it is now known that the beneficial effects of MSCs depend, at least in part, on their secretome, referring to all the bioactive molecules (neurotrophic factors) released in the conditioned medium (CM) or in the extracellular vesicles (EVs) in particular exosomes (Exos). In this review, we described the similarities and differences between various DSCs. Our focus was on the secretome of DSCs and their applications in cell therapy for neurological disorders. For neuro-regenerative purposes, the secretome of different DSCs has been tested. Among these, the secretome of dental pulp stem cells and stem cells from human exfoliated deciduous teeth have been the most widely studied. Both CM and Exos obtained from DSCs have been shown to promote neurite outgrowth and neuroprotective effects as well as their combination with scaffold materials (to improve their functional integration in the tissue). For these reasons, the secretome obtained from DSCs in combination with scaffold materials may represent a promising tissue engineering approach for neuroprotective and neuro-regenerative treatments.
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Affiliation(s)
- Francesca Santilli
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Jessica Fabrizi
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Costantino Santacroce
- Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", Via A.M. Ricci 35/A, 02100, Rieti, Italy
| | - Daniela Caissutti
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Zaira Spinello
- Department of Experimental Medicine, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy
| | - Niccolò Candelise
- National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 29900161, Rome, Italy
| | - Loreto Lancia
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Fanny Pulcini
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy
| | - Simona Delle Monache
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
| | - Vincenzo Mattei
- Dipartimento di Scienze della Vita, della Salute e delle Professioni Sanitarie, Link Campus University, Via del Casale di San Pio V 44, 00165, Rome, Italy.
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25
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Xu K, Li YD, Ren LY, Song HL, Yang QY, Xu DL. Long non-coding RNA X-Inactive Specific Transcript (XIST) interacting with USF2 promotes osteogenic differentiation of periodontal ligament stem cells through regulation of WDR72 transcription. J Periodontal Res 2023; 58:1235-1247. [PMID: 37712743 DOI: 10.1111/jre.13179] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 07/27/2023] [Accepted: 08/17/2023] [Indexed: 09/16/2023]
Abstract
BACKGROUND Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. METHODS Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs. CONCLUSION WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis.
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Affiliation(s)
- Ke Xu
- Department of Stomatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Ya-Dong Li
- Department of Stomatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Liu-Yang Ren
- Department of Stomatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Hai-Long Song
- Department of Stomatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Qiao-Yun Yang
- Department of Stomatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Dong-Liang Xu
- Department of Stomatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
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26
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Okić Đorđević I, Kukolj T, Živanović M, Momčilović S, Obradović H, Petrović A, Mojsilović S, Trivanović D, Jauković A. The Role of Doxycycline and IL-17 in Regenerative Potential of Periodontal Ligament Stem Cells: Implications in Periodontitis. Biomolecules 2023; 13:1437. [PMID: 37892119 PMCID: PMC10604178 DOI: 10.3390/biom13101437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 09/18/2023] [Accepted: 09/21/2023] [Indexed: 10/29/2023] Open
Abstract
Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism. In the present study, we aimed to determine whether Dox can affect the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) modulated by IL-17 in terms of cell migration, osteogenic potential, bioenergetics and expression of extracellular matrix metalloproteinase 2 (MMP-2). Our findings indicate that Dox reduces the stimulatory effect of IL-17 on migration and MMP-2 expression in PDLSCs. Furthermore, Dox stimulates osteogenic differentiation of PDLSCs, annulling the inhibitory effect of IL-17 on PDLSCs osteogenesis. In addition, analyses of mitochondrial respiration reveal that Dox decreases oxygen consumption rate in PDLSCs exposed to IL-17, suggesting that changes in metabolic performance can be involved in Dox-mediated effects on PDLSCs. The pro-regenerative properties of Dox in inflammatory microenvironment candidates Dox in terms of regenerative therapy of PD-affected periodontium are observed.
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Affiliation(s)
- Ivana Okić Đorđević
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Tamara Kukolj
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Milena Živanović
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Sanja Momčilović
- Group for Neuroendocrinology, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Hristina Obradović
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Anđelija Petrović
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Slavko Mojsilović
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Drenka Trivanović
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
| | - Aleksandra Jauković
- Group for Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia
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27
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Jia L, Zhang Y, Sun S, Hao X, Wen Y. Dasatinib regulates the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals. Int J Med Sci 2023; 20:1460-1468. [PMID: 37790842 PMCID: PMC10542188 DOI: 10.7150/ijms.87089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 08/31/2023] [Indexed: 10/05/2023] Open
Abstract
Periodontal ligament stem cells (PDLSCs) are important candidate seed cells for alveolar bone tissue engineering. Dasatinib is a tyrosine kinase inhibitor, and its influence on the osteogenic differentiation of mesenchymal stem cells is a controversial topic. The present study explored the effects of different concentrations of dasatinib on the proliferation and osteogenic differentiation of PDLSCs and tentatively revealed the related mechanism. The results of CCK8 showed that low concentrations of dasatinib (1 nM) did not affect proliferation, while high concentrations of dasatinib significantly inhibited the proliferative activity of PDLSCs. This could be related to the inhibiting effects of dasatinib on Erk signals. ALP staining, alizarin red staining, and western blot proved that low concentrations of dasatinib (1 nM) promoted the osteogenic differentiation of PDLSCs, while high concentrations of dasatinib inhibited it. The negative effects of dasatinib on osteogenic differentiation were reversed when EID3 was knocked down, suggesting that EID3 mediates the regulation of dasatinib on the osteo-differentiation of PDLSCs. Taken together, high concentrations of dasatinib inhibited the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals, while low concentrations of dasatinib could be a potential method to enhance the bone regeneration ability of PDLSCs.
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Affiliation(s)
- Linglu Jia
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong, China
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong, China
- Shandong Provincial Clinical Research Center for Oral Diseases, Shandong, China
| | - Yafei Zhang
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong, China
- Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China & Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
| | - Shaoqing Sun
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong, China
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong, China
- Shandong Provincial Clinical Research Center for Oral Diseases, Shandong, China
| | - Xingyao Hao
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong, China
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong, China
- Shandong Provincial Clinical Research Center for Oral Diseases, Shandong, China
| | - Yong Wen
- School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong, China
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong, China
- Shandong Provincial Clinical Research Center for Oral Diseases, Shandong, China
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28
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McMillan A, McMillan N, Gupta N, Kanotra SP, Salem AK. 3D Bioprinting in Otolaryngology: A Review. Adv Healthc Mater 2023; 12:e2203268. [PMID: 36921327 PMCID: PMC10502192 DOI: 10.1002/adhm.202203268] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 03/05/2023] [Indexed: 03/17/2023]
Abstract
The evolution of tissue engineering and 3D bioprinting has allowed for increased opportunities to generate musculoskeletal tissue grafts that can enhance functional and aesthetic outcomes in otolaryngology-head and neck surgery. Despite literature reporting successes in the fabrication of cartilage and bone scaffolds for applications in the head and neck, the full potential of this technology has yet to be realized. Otolaryngology as a field has always been at the forefront of new advancements and technology and is well poised to spearhead clinical application of these engineered tissues. In this review, current 3D bioprinting methods are described and an overview of potential cell types, bioinks, and bioactive factors available for musculoskeletal engineering using this technology is presented. The otologic, nasal, tracheal, and craniofacial bone applications of 3D bioprinting with a focus on engineered graft implantation in animal models to highlight the status of functional outcomes in vivo; a necessary step to future clinical translation are reviewed. Continued multidisciplinary efforts between material chemistry, biological sciences, and otolaryngologists will play a key role in the translation of engineered, 3D bioprinted constructs for head and neck surgery.
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Affiliation(s)
- Alexandra McMillan
- Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, IA
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA
| | - Nadia McMillan
- Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
| | - Nikesh Gupta
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA
| | - Sohit P. Kanotra
- Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, IA
| | - Aliasger K. Salem
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA
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Purwaningrum M, Giachelli CM, Osathanon T, Rattanapuchpong S, Sawangmake C. Dissecting specific Wnt components governing osteogenic differentiation potential by human periodontal ligament stem cells through interleukin-6. Sci Rep 2023; 13:9055. [PMID: 37270571 PMCID: PMC10239497 DOI: 10.1038/s41598-023-35569-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 05/20/2023] [Indexed: 06/05/2023] Open
Abstract
Periodontal ligament stem cells (PDLSCs) play a significant role on periodontal tissue and alveolar bone homeostasis. During inflammation, interleukin (IL)-6 serves as one of key cytokine players controlling tissue reaction as well as alveolar bone tissue remodeling. It is believed that periodontal tissue inflammation causes periodontium degradation, especially alveolar bone. However, in this study, we show that an inflammatory mediator, IL-6, may serve another direction on alveolar bone homeostasis during inflammatory condition. We found that, IL-6 at 10 and 20 ng/mL was not cytotoxic and dose-dependently exerted beneficial effects on osteogenic differentiation of human PDLSCs (hPDLSCs), as demonstrated by increased alkaline phosphatase activity, mRNA expression of osteogenic markers, and matrix mineralization. The presence of physiological and inflammatory level of IL-6, the osteogenic differentiation potential by hPDLSCs was enhanced by several possible mechanisms including transforming growth factor (TGF), Wnt, and Notch pathways. After in-depth and thorough exploration, we found that Wnt pathway serves as key regulator controlling osteogenic differentiation by hPDLSCs amid the IL-6 presentation. Surprisingly, apart from other mesenchymal stem cells, distinct Wnt components are employed by hPDLSCs, and both canonical and non-canonical Wnt pathways are triggered by different mechanisms. Further validation by gene silencing, treatment with recombinant Wnt ligands, and β-catenin stabilization/translocation confirmed that IL-6 governed the canonical Wnt/β-catenin pathway via either WNT2B or WNT10B and employed WNT5A to activate the non-canonical Wnt pathway. These findings fulfill the homeostasis pathway governing periodontal tissue and alveolar bone regeneration and may serve for further therapeutic regimen design for restoring the tissues.
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Affiliation(s)
- Medania Purwaningrum
- The International Graduate Program of Veterinary Science and Technology (VST), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Department of Biochemistry, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
- Veterinary Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Cecilia M Giachelli
- Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA
| | - Thanaphum Osathanon
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand
- Center of Excellence in Regenerative Dentistry (CERD), Chulalongkorn University, Bangkok, 10330, Thailand
| | - Sirirat Rattanapuchpong
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
- Veterinary Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
- Academic Affairs, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
| | - Chenphop Sawangmake
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
- Veterinary Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
- Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
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The Role and Involvement of Stem Cells in Periodontology. Biomedicines 2023; 11:biomedicines11020387. [PMID: 36830924 PMCID: PMC9953576 DOI: 10.3390/biomedicines11020387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
Periodontitis is a widespread inflammatory condition, characterized by a progressive deterioration of the supporting structures of the teeth. Due to the complexity of periodontal tissue and the surrounding inflammatory microenvironment, the repair of lesions at this level represents a continuous challenge. The regeneration of periodontal tissues is considered a promising strategy. Stem cells have remarkable properties, such as immunomodulatory potential, proliferation, migration, and multilineage differentiation. Thus, they can be used to repair tissue damage and reduce inflammation, potentially leading to periodontal regeneration. Among the stem cells used for periodontal regeneration, we studied dental mesenchymal stem cells (DMSCs), non-dental stem cells, and induced pluripotent stem cells (IPSCs). Although these cells have well documented important physiological characteristics, their use in contemporary practice to repair the affected periodontium is still a challenge.
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Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends. Int J Mol Sci 2022; 23:ijms232415492. [PMID: 36555133 PMCID: PMC9779866 DOI: 10.3390/ijms232415492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/24/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes-especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future.
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Zhao Z, Liu J, Weir MD, Schneider A, Ma T, Oates TW, Xu HHK, Zhang K, Bai Y. Periodontal ligament stem cell-based bioactive constructs for bone tissue engineering. Front Bioeng Biotechnol 2022; 10:1071472. [PMID: 36532583 PMCID: PMC9755356 DOI: 10.3389/fbioe.2022.1071472] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 11/17/2022] [Indexed: 09/29/2023] Open
Abstract
Objectives: Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially for maxillofacial bone and periodontal regeneration. Many studies have shown potent results via PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration. Data and sources: An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers. Results: Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture. Conclusoin: This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.
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Affiliation(s)
- Zeqing Zhao
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Jin Liu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, China
| | - Michael D. Weir
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Tao Ma
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - Thomas W. Oates
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
| | - Hockin H. K. Xu
- Biomaterials and Tissue Engineering Division, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD, United States
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States
- Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Ke Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
| | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, China
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Jin S, Jiang H, Sun Y, Li F, Xia J, Li Y, Zheng J, Qin Y. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments. Open Life Sci 2022; 17:1240-1248. [PMID: 36213382 PMCID: PMC9490861 DOI: 10.1515/biol-2022-0474] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 06/29/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
Periodontitis is a common disease that is difficult to treat, and if not controlled in time, it causes severe conditions, such as alveolar bone resorption and tooth loosening and loss. Periodontal ligament stem cells constitute a promising cell source for regenerative treatment of periodontitis due to their high osteogenic differentiation capacity. PDLSC osteogenesis plays a central role in periodontal regeneration through successive cytokine-mediated signaling pathways and various biochemical and physicochemical factors. However, this process is inhibited in the inflammatory periodontitis environment due to high concentrations of lipopolysaccharide. Here, we review the mechanisms that influence the osteogenic differentiation of periodontal stem cells in this inflammatory microenvironment.
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Affiliation(s)
- Shenghao Jin
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
| | - Haitao Jiang
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
| | - Yue Sun
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
| | - Fang Li
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
| | - Jianglan Xia
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
| | - Yaxin Li
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
| | - Jiwei Zheng
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
| | - Ying Qin
- Department of Periodontics, School of Stomatology, Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Xuzhou Medical University , Xuzhou , Jiangsu, 221000 , China
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Ahuja A, Tyagi PK, Kumar M, Sharma N, Prakash S, Radha, Chandran D, Dhumal S, Rais N, Singh S, Dey A, Senapathy M, Saleena LAK, Shanavas A, Mohankumar P, Rajalingam S, Murugesan Y, Vishvanathan M, Sathyaseelan SK, Viswanathan S, Kumar KK, Natta S, Mekhemar M. Botanicals and Oral Stem Cell Mediated Regeneration: A Paradigm Shift from Artificial to Biological Replacement. Cells 2022; 11:2792. [PMID: 36139367 PMCID: PMC9496740 DOI: 10.3390/cells11182792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/03/2022] [Accepted: 09/04/2022] [Indexed: 11/23/2022] Open
Abstract
Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.
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Affiliation(s)
- Anami Ahuja
- Department of Biotechnology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow 226031, India
- Department of Biotechnology, Meerut Institute of Engineering and Technology, Meerut 250005, India
| | - Pankaj Kumar Tyagi
- Department of Biotechnology, Noida Institute of Engineering & Technology, Greater Noida 201306, India
| | - Manoj Kumar
- Chemical and Biochemical Processing Division, ICAR–Central Institute for Research on Cotton Technology, Mumbai 400019, India
| | - Naveen Sharma
- Division of Biomedical Informatics, Indian Council of Medical Research, New Delhi 110029, India
| | - Suraj Prakash
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Radha
- School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, India
| | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sci-ences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Sangram Dhumal
- Division of Horticulture, RCSM College of Agriculture, Kolhapur 416004, India
| | - Nadeem Rais
- Department of Pharmacy, Bhagwant University, Ajmer 305004, India
| | - Surinder Singh
- Dr. S. S. Bhatnagar University Institute of Chemical Engineering and Technology, Panjab University, Chandigarh 160014, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, India
| | - Marisennayya Senapathy
- Department of Rural Development and Agricultural Extension, College of Agriculture, Wolaita Sodo University, Wolaita Sodo P.O. Box 138, Ethiopia
| | - Lejaniya Abdul Kalam Saleena
- Department of Food Science and Nutrition, Faculty of Applied Sciences, UCSI University, Kuala Lampur 56000, Malaysia
| | - Arjun Shanavas
- Division of Medicine, Indian Veterinary Research Institute, Bareilly 243122, India
| | - Pran Mohankumar
- School of Agriculture and Biosciences, Karunya Institute of Technology and Sciences, Coimbatore 641114, India
| | - Sureshkumar Rajalingam
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Yasodha Murugesan
- Department of Agronomy, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Marthandan Vishvanathan
- Department of Seed Science and Technology, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | | | - Sabareeshwari Viswanathan
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Keerthana Krishna Kumar
- Department of Soil Science and Agricultural Chemistry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Suman Natta
- ICAR—National Research Centre for Orchids, Pakyong 737106, India
| | - Mohamed Mekhemar
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Chris-tian-Albrecht’s University, 24105 Kiel, Germany
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Dai Z, Li Z, Zheng W, Yan Z, Zhang L, Yang J, Xiao J, Sun H, Li S, Huang W. Gallic Acid Ameliorates the Inflammatory State of Periodontal Ligament Stem Cells and Promotes Pro-Osteodifferentiation Capabilities of Inflammatory Stem Cell-Derived Exosomes. Life (Basel) 2022; 12:1392. [PMID: 36143428 PMCID: PMC9501550 DOI: 10.3390/life12091392] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/22/2022] [Accepted: 09/02/2022] [Indexed: 11/20/2022] Open
Abstract
The slow proliferation rate and poor osteodifferentiation ability of inflammatory periodontal membrane stem cells extracted from periodontitis tissues (i-PDLSCs) account for poor efficiency in treating inflammatory bone loss. Exosomes reportedly have inducible and relatively stable components, allowing them to promote inflammatory bone repair, but obtaining i-PDLSCs exosomes with the ability to promote osteodifferentiation is challenging. In the present study, i-PDLSCs were extracted from periodontal membrane tissues of patients with severe periodontitis, and in vitro induction with gallic acid (GA) significantly promoted the proliferative activity of i-PDLSCs at a concentration of 10 mM, with TC0 of 11.057 mM and TC50 of 67.56 mM for i-PDLSCs. After mRNA sequencing, we found that GA could alleviate oxidative stress in i-PDLSCs and increase its mitochondrial membrane potential and glucose aerobic metabolism level, thus promoting the osteodifferentiation of i-PDLSCs. After exosomes of i-PDLSCs after GA induction (i-EXO-GA) were isolated by differential centrifugation, we found that 200 ug/mL of i-EXO-GA could remarkably promote the osteodifferentiation of i-PDLSCs. Overall, our results suggest that GA induction can enhance the proliferation and osteodifferentiation in primary cultures of i-PDLSCs in vitro, mediated by alleviating oxidative stress and glycometabolism levels in cells, which further influences the osteodifferentiation-promoting ability of i-EXO-GA. Overall, we provide a viable cell and exosome induction culture method for treating inflammatory alveolar defects associated with periodontitis.
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Affiliation(s)
- Zhenning Dai
- Department of Stomatology, Guangdong Key Laboratory of Traditional Chinese Medicine Research and Development, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou 510095, China
| | - Ziyue Li
- Guangdong Medical Innovation Platform for Translation of 3D Printing Application, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510630, China
- Department of Anatomy, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Weihan Zheng
- Guangdong Medical Innovation Platform for Translation of 3D Printing Application, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510630, China
- Department of Anatomy, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Zi Yan
- Guangdong Medical Innovation Platform for Translation of 3D Printing Application, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510630, China
- Department of Anatomy, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Lijun Zhang
- Institute of Genomic Medicine, College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Jiaxin Yang
- Department of Anatomy, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jing Xiao
- Division of Spine Surgery, Section II, Department of Orthopedics, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510630, China
| | - Hanxiao Sun
- Institute of Genomic Medicine, College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Shiyu Li
- Guangdong Medical Innovation Platform for Translation of 3D Printing Application, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510630, China
- Department of Anatomy, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Wenhua Huang
- Guangdong Medical Innovation Platform for Translation of 3D Printing Application, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou 510630, China
- Department of Anatomy, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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36
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Swanson WB, Yao Y, Mishina Y. Novel approaches for periodontal tissue engineering. Genesis 2022; 60:e23499. [PMID: 36086991 PMCID: PMC9787372 DOI: 10.1002/dvg.23499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 08/11/2022] [Accepted: 08/12/2022] [Indexed: 12/30/2022]
Abstract
The periodontal complex involves the hard and soft tissues which support dentition, comprised of cementum, bone, and the periodontal ligament (PDL). Periodontitis, a prevalent infectious disease of the periodontium, threatens the integrity of these tissues and causes irreversible damage. Periodontal therapy aims to repair and ultimately regenerate these tissues toward preserving native dentition and improving the physiologic integration of dental implants. The PDL contains multipotent stem cells, which have a robust capacity to differentiate into various types of cells to form the PDL, cementum, and alveolar bone. Selection of appropriate growth factors and biomaterial matrices to facilitate periodontal regeneration are critical to recapitulate the physiologic organization and function of the periodontal complex. Herein, we discuss the current state of clinical periodontal regeneration including a review of FDA-approved growth factors. We will highlight advances in preclinical research toward identifying additional growth factors capable of robust repair and biomaterial matrices to augment regeneration similarly and synergistically, ultimately improving periodontal regeneration's predictability and long-term efficacy. This review should improve the readers' understanding of the molecular and cellular processes involving periodontal regeneration essential for designing comprehensive therapeutic approaches.
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Affiliation(s)
- W. Benton Swanson
- Department of Biologic and Materials Science, Division of ProsthodonticsUniversity of Michigan School of DentistryAnn ArborMichiganUSA
| | - Yao Yao
- Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMichiganUSA,Biointerfaces InstituteUniversity of MichiganAnn ArborMichiganUSA
| | - Yuji Mishina
- Department of Biologic and Materials Science, Division of ProsthodonticsUniversity of Michigan School of DentistryAnn ArborMichiganUSA
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Zhang S, Zhang L, Lu H, Yao Y, Liu X, Hou J. A cuproptosis and copper metabolism–related gene prognostic index for head and neck squamous cell carcinoma. Front Oncol 2022; 12:955336. [PMID: 36072790 PMCID: PMC9441563 DOI: 10.3389/fonc.2022.955336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 08/01/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundThe purpose of this study was to identify the prognostic value of cuproptosis and copper metabolism–related genes, to clarify their molecular and immunological characteristics, and to elucidate their benefits in head and neck squamous cell carcinoma (HNSCC).MethodsThe details of human cuproptosis and copper metabolism–related genes were searched and filtered from the msigdb database and the latest literature. To identify prognostic genes associated with cuproptosis and copper metabolism, we used least absolute shrinkage and selection operator regression, and this coefficient was used to set up a prognostic risk score model. HNSCC samples were divided into two groups according to the median risk. Afterwards, the function and immune characteristics of these genes in HNSCC were analyzed.ResultsThe 14-gene signature was constructed to classify HNSCC patients into low-risk and high-risk groups according to the risk level. In the The Cancer Genome Atlas (TCGA) cohort, the overall survival (OS) rate of the high-risk group was lower than that of the low-risk group (P < 0.0001). The area under the curve of the time-dependent Receiver Operator Characteristic (ROC) curve assessed the good performance of the genetic signature in predicting OS and showed similar performance in the external validation cohort. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays and Protein-Protein Interaction (PPI) protein networks have been used to explore signaling pathways and potential mechanisms that were markedly active in patients with HNSCC. Furthermore, the 14 cuproptosis and copper metabolism-related genes were significantly correlated with the immune microenvironment, suggesting that these genes may be linked with the immune regulation and development of HNSCC.ConclusionsOur results emphasize the significance of cuproptosis and copper metabolism as a predictive biomarker for HNSCC, and its expression levels seem to be correlated with immune- related features; thus, they may be a possible biomarker for HNSCC prognosis.
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Affiliation(s)
- Shuaiyuan Zhang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Lujin Zhang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Huanzi Lu
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Yihuan Yao
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Xiaoyong Liu
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Jingsong Hou
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Jingsong Hou,
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Novel In Situ-Cross-Linked Electrospun Gelatin/Hydroxyapatite Nonwoven Scaffolds Prove Suitable for Periodontal Tissue Engineering. Pharmaceutics 2022; 14:pharmaceutics14061286. [PMID: 35745858 PMCID: PMC9230656 DOI: 10.3390/pharmaceutics14061286] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/03/2022] [Accepted: 06/14/2022] [Indexed: 12/23/2022] Open
Abstract
Periodontal diseases affect millions of people worldwide and can result in tooth loss. Regenerative treatment options for clinical use are thus needed. We aimed at developing new nonwoven-based scaffolds for periodontal tissue engineering. Nonwovens of 16% gelatin/5% hydroxyapatite were produced by electrospinning and in situ glyoxal cross-linking. In a subset of scaffolds, additional porosity was incorporated via extractable polyethylene glycol fibers. Cell colonization and penetration by human mesenchymal stem cells (hMSCs), periodontal ligament fibroblasts (PDLFs), or cocultures of both were visualized by scanning electron microscopy and 4′,6-diamidin-2-phenylindole (DAPI) staining. Metabolic activity was assessed via Alamar Blue® staining. Cell type and differentiation were analyzed by immunocytochemical staining of Oct4, osteopontin, and periostin. The electrospun nonwovens were efficiently populated by both hMSCs and PDLFs, while scaffolds with additional porosity harbored significantly more cells. The metabolic activity was higher for cocultures of hMSCs and PDLFs, or for PDLF-seeded scaffolds. Periostin and osteopontin expression was more pronounced in cocultures of hMSCs and PDLFs, whereas Oct4 staining was limited to hMSCs. These novel in situ-cross-linked electrospun nonwoven scaffolds allow for efficient adhesion and survival of hMSCs and PDLFs. Coordinated expression of differentiation markers was observed, which rendered this platform an interesting candidate for periodontal tissue engineering.
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Li ZB, Yang HQ, Li K, Yin Y, Feng SS, Ge SH, Yu Y. Comprehensive Transcriptome Analysis of mRNA Expression Patterns Associated With Enhanced Biological Functions in Periodontal Ligament Stem Cells Subjected to Short-Term Hypoxia Pretreatment. Front Genet 2022; 13:797055. [PMID: 35211157 PMCID: PMC8861432 DOI: 10.3389/fgene.2022.797055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 01/13/2022] [Indexed: 11/20/2022] Open
Abstract
Short-term hypoxia pretreatment significantly enhances periodontal ligament stem cell (PDLSC)-based periodontal tissue regeneration by improving various cellular biological functions, but the underlying mechanisms remain unclear. In this study, based on RNA sequencing (RNA-seq), we comprehensively analyzed the possible regulatory mechanisms of the short-term hypoxic effects on the biological functions of healthy and inflammatory PDLSCs. A total of 134 and 164 differentially expressed genes (DEGs) were identified under healthy and inflammatory conditions, respectively. Functional enrichment analyses indicated that DEGs under both conditions share certain biological processes and pathways, including metabolic processes, developmental processes, reproductive processes, localization, immune system processes and the HIF-1 signaling pathway. The DEGs identified under inflammatory conditions were more significantly enriched in cell cycle-related processes and immune-related pathways, while DEGs identified under healthy condition were more significantly enriched in the TGF-β signaling pathway. A protein-protein interaction network analysis of the 59 DEGs in both conditions was performed, and 15 hub genes were identified. These hub genes were mainly involved in glycolysis, the cellular response to hypoxia, cell differentiation, and immune system processes. In addition, we found that hypoxia induced significant differential expression of genes associated with proliferation, differentiation, migration, apoptosis and immunoregulation under both healthy and inflammatory conditions. This study provides comprehensive insights into the effects of short-term hypoxia on the biological functions of PDLSCs and suggests a potentially feasible strategy for improving the clinical effectiveness of cell-based periodontal tissue engineering.
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Affiliation(s)
- Zhi-Bang Li
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China.,State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Hui-Qi Yang
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Kun Li
- Department of Periodontology, Jinan Stomatological Hospital, Jinan, China
| | - Yuan Yin
- State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Su-Su Feng
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shao-Hua Ge
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yang Yu
- Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, China
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Ye Y, Ke Y, Liu L, Xiao T, Yu J. CircRNA FAT1 Regulates Osteoblastic Differentiation of Periodontal Ligament Stem Cells via miR-4781-3p/SMAD5 Pathway. Stem Cells Int 2021; 2021:5177488. [PMID: 35003269 PMCID: PMC8731273 DOI: 10.1155/2021/5177488] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 11/19/2021] [Accepted: 12/04/2021] [Indexed: 12/13/2022] Open
Abstract
The ability of human periodontal ligament stem cells (PDLSCs) to differentiate into osteoblasts is significant in periodontal regeneration tissue engineering. In this study, we explored the role and mechanism of circRNA FAT1 (circFAT1) in the osteogenic differentiation of human PDLSCs. The proliferation capacity of PDLSCs was evaluated by EdU and CCK-8 assay. The abilities of circFAT1 and miR-4781-3p in regulating PDLSC differentiation were analyzed by western blot, reverse transcription-polymerase chain reaction (RT-PCR), alkaline phosphatase (ALP), and Alizarin red staining (ARS). A nucleocytoplasmic separation experiment was utilized for circFAT1 localization. A dual-luciferase reporter assay confirmed the binding relationship between miR-4781-3p and circFAT1. It was showed that circFAT1 does not affect the proliferation of PDLSCs. The osteogenic differentiation of PDLSCs was benefited from circFAT1, which serves as a miRNA sponge for miR-4781-3p targeting SMAD5. Both knockdown of circFAT1 and overexpression of miR-4781-3p suppressed the osteogenic differentiation of PDLSCs. Thus, circFAT1 might be considered as a potential target of PDLSCs mediated periodontal bone regeneration.
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Affiliation(s)
- Yu Ye
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Yue Ke
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Liu Liu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Tong Xiao
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
| | - Jinhua Yu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University & Department of Endodontic, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
- Institute of Stomatology, Nanjing Medical University, Nanjing, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China
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Abstract
Technological innovations in cellular and molecular aspects of tissue engineering --scaffolds, stem cells and 3D printed tissues --have been dramatically increased in the last decade. However, regenerative treatment still has challenges in translation to clinic. This is partly due to failure of addressing an essential element of wound healing, inflammation. It is now well-recognized that inflammation is an active process. This paradigm shift opened up a new avenue of therapeutic approaches called "host-modulation." Host-modulation therapies capable of modulating inflammatory response at multiple levels and mimicking the natural sequence of wound healing offer a new direction and promising clinical translation.
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Bar JK, Lis-Nawara A, Grelewski PG. Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential. Int J Mol Sci 2021; 22:ijms222112018. [PMID: 34769446 PMCID: PMC8584775 DOI: 10.3390/ijms222112018] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/02/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of the bioactive factors secreted by human dental pulp stem cells (hDPSCs) and human exfoliated deciduous teeth (SHEDs) is not completely understood. In this review, we outline the current data on the hDPSC- and SHED-derived secretome as a potential candidate in the regeneration of bone, cartilage, and nerve tissue. Published reports demonstrate that the dental MSC-derived secretome/conditional medium may be effective in treating neurodegenerative diseases, neural injuries, cartilage defects, and repairing bone by regulating neuroprotective, anti-inflammatory, antiapoptotic, and angiogenic processes through secretome paracrine mechanisms. Dental MSC-secretomes, similarly to the bone marrow MSC-secretome activate molecular and cellular mechanisms, which determine the effectiveness of cell-free therapy. Many reports emphasize that dental MSC-derived secretomes have potential application in tissue-regenerating therapy due to their multidirectional paracrine effect observed in the therapy of many different injured tissues.
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Stem Cells and Their Derivatives-Implications for Alveolar Bone Regeneration: A Comprehensive Review. Int J Mol Sci 2021; 22:ijms222111746. [PMID: 34769175 PMCID: PMC8583713 DOI: 10.3390/ijms222111746] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 10/25/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
Oral and craniofacial bone defects caused by congenital disease or trauma are widespread. In the case of severe alveolar bone defect, autologous bone grafting has been considered a “gold standard”; however, the procedure has several disadvantages, including limited supply, resorption, donor site morbidity, deformity, infection, and bone graft rejection. In the last few decades, bone tissue engineering combined with stem cell-based therapy may represent a possible alternative to current bone augmentation techniques. The number of studies investigating different cell-based bone tissue engineering methods to reconstruct alveolar bone damage is rapidly rising. As an interdisciplinary field, bone tissue engineering combines the use of osteogenic cells (stem cells/progenitor cells), bioactive molecules, and biocompatible scaffolds, whereas stem cells play a pivotal role. Therefore, our work highlights the osteogenic potential of various dental tissue-derived stem cells and induced pluripotent stem cells (iPSCs), the progress in differentiation techniques of iPSCs into osteoprogenitor cells, and the efforts that have been made to fabricate the most suitable and biocompatible scaffold material with osteoinductive properties for successful bone graft generation. Moreover, we discuss the application of stem cell-derived exosomes as a compelling new form of “stem-cell free” therapy.
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