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1
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Wang Y, Ge H, Chen P, Wang Y. Wnt/β-catenin signaling in corneal epithelium development, homeostasis, and pathobiology. Exp Eye Res 2024; 246:110022. [PMID: 39117134 DOI: 10.1016/j.exer.2024.110022] [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: 04/18/2024] [Revised: 07/07/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
The corneal epithelium is located on the most anterior surface of the eyeball and protects against external stimuli. The development of the corneal epithelium and the maintenance of corneal homeostasis are essential for the maintenance of visual acuity. It has been discovered recently via the in-depth investigation of ocular surface illnesses that the Wnt/β-catenin signaling pathway is necessary for the growth and stratification of corneal epithelial cells as well as the control of endothelial cell stability. In addition, the Wnt/β-catenin signaling pathway is directly linked to the development of common corneal illnesses such as keratoconus, fungal keratitis, and corneal neovascularization. This review mainly summarizes the role of the Wnt/β-catenin signaling pathway in the development, homeostasis, and pathobiology of cornea, hoping to provide new insights into the study of corneal epithelium and the treatment of related diseases.
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Affiliation(s)
- Yihui Wang
- School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Huanhuan Ge
- School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Peng Chen
- School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China; Institute of Stem Cell Regeneration Medicine, School of Basic Medicine, Qingdao University, Qingdao, 266071, China.
| | - Ye Wang
- Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao, Shandong 266042, China.
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2
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Chouaib B, Cuisinier F, Collart-Dutilleul PY. Dental stem cell-conditioned medium for tissue regeneration: Optimization of production and storage. World J Stem Cells 2022; 14:287-302. [PMID: 35662860 PMCID: PMC9136565 DOI: 10.4252/wjsc.v14.i4.287] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/19/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSC) effects on tissue regeneration are mainly mediated by their secreted substances (secretome), inducing their paracrine activity. This Conditioned medium (CM), including soluble factors (proteins, nucleic acids, lipids) and extracellular vesicles is emerging as a potential alternative to cell therapy. However, the manufacturing of CM suffers from variable procedures and protocols leading to varying results between studies. Besides, there is no well-defined optimized procedure targeting specific applications in regenerative medicine. AIM To focus on conditioned medium produced from dental MSC (DMSC-CM), we reviewed the current parameters and manufacturing protocols, in order to propose a standardization and optimization of these manufacturing procedures. METHODS We have selected all publications investigating the effects of dental MSC secretome in in vitro and in vivo models of tissue regeneration, in accordance with the PRISMA guidelines. RESULTS A total of 351 results were identified. And based on the inclusion criteria described above, 118 unique articles were included in the systematic review. DMSC-CM production was considered at three stages: before CM recovery (cell sources for CM), during CM production (culture conditions) and after production (CM treatment). CONCLUSION No clear consensus could be recovered as evidence-based methods, but we were able to describe the most commonly used protocols: donors under 30 years of age, dental pulp stem cells and exfoliated deciduous tooth stem cells with cell passage between 1 and 5, at a confluence of 70% to 80%. CM were often collected during 48 h, and stored at -80 °C. It is important to point out that the preconditioning environment had a significant impact on DMSC-CM content and efficiency.
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Affiliation(s)
- Batoul Chouaib
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
| | - Frédéric Cuisinier
- Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
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3
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Akhtar M, Woo KM, Tahir M, Wu W, Elango J, Mirza MR, Khan M, Shamim S, Arany PR, Rahman SU. Enhancing osteoblast differentiation through small molecule-incorporated engineered nanofibrous scaffold. Clin Oral Investig 2022; 26:2607-2618. [PMID: 34677694 DOI: 10.1007/s00784-021-04230-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 10/13/2021] [Indexed: 12/20/2022]
Abstract
OBJECTIVE This study aimed to investigate the effect of small molecules incorporated into the engineered nanofibrous scaffold to enhance the osteoblast differentiation MATERIALS AND METHODS: Poly-ε-caprolactone (PCL) nanofiber matrices with lithium chloride (LiCl) were fabricated using the electrospinning technique. Scaffolds were characterized using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX). Scaffolds were seeded with MC3T3-E1 cells and assessed using Western blots (β-catenin), alamarBlue assay (proliferation), qPCR (osteoblast differentiation), and mineralization (Alizarin Red staining). RESULTS We observed LiCl nanofiber scaffolds induced concentration-dependent cell proliferation that correlated with an increased β-catenin expression indicating sustained Wnt signaling. Next, we examined osteoblast differentiation markers such as osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) and noted increased expression in LiCl nanofiber scaffolds. We also noted increased bone morphogenetic protein (BMP-2, 4, and 7) expressions suggesting activated Wnt can promote cures to further osteogenic differentiation. Finally, Alizarin Red staining demonstrated increased mineral deposition in LiCl-incorporated nanofiber scaffolds. CONCLUSIONS Together, these results indicated that LiCl-incorporated nanofiber scaffolds enhance osteoblast differentiation. CLINICAL RELEVANCE Small molecule-incorporated nanofibrous scaffolds are an innovative clinical tool for bone tissue engineering.
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Affiliation(s)
- Maria Akhtar
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
- Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan
| | - Kyung Mi Woo
- Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, 08826, Republic of Korea
| | - Muhammad Tahir
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
| | - Wenhui Wu
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China
| | - Jeevithan Elango
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China
| | - Munazza R Mirza
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
| | - Maryam Khan
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Saba Shamim
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Praveen R Arany
- Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA
| | - Saeed Ur Rahman
- Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan.
- Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA.
- Oral Biology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, 45000, Pakistan.
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4
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Liu S, Sun J, Yuan S, Yang Y, Gong Y, Wang Y, Guo R, Zhang X, Liu Y, Mi H, Wang M, Liu M, Li R. Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling. Bioact Mater 2022; 7:85-97. [PMID: 34466719 PMCID: PMC8379347 DOI: 10.1016/j.bioactmat.2021.05.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 04/03/2021] [Accepted: 05/14/2021] [Indexed: 12/26/2022] Open
Abstract
Treated dentin matrix (TDM) is an ideal scaffold material containing multiple extracellular matrix factors. The canonical Wnt signaling pathway is necessary for tooth regeneration. Thus, this study investigated whether the TDM can promote the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and determined the potential role of Wnt/β-catenin signaling in this process. Different concentrations of TDM promoted the dental differentiation of the hDPSCs and meanwhile, the expression of GSK3β was decreased. Of note, the expression of the Wnt/β-catenin pathway-related genes changed significantly in the context of TDM induction, as per RNA sequencing (RNA seq) data. In addition, the experiment showed that new dentin was visible in rat mandible cultured with TDM, and the thickness was significantly thicker than that of the control group. In addition, immunohistochemical staining showed lower GSK3β expression in new dentin. Consistently, the GSK3β knockdown hDPSCs performed enhanced odotogenesis compared with the control groups. However, GSK3β overexpressing could decrease odotogenesis of TDM-induced hDPSCs. These results were confirmed in immunodeficient mice and Wistar rats. These suggest that TDM promotes odontogenic differentiation of hDPSCs by directly targeting GSK3β and activating the canonical Wnt/β-catenin signaling pathway and provide a theoretical basis for tooth regeneration engineering.
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Affiliation(s)
- Sirui Liu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences at Zhengzhou University, Zhengzhou, China
| | - Jingjing Sun
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuai Yuan
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yanyu Yang
- College of Materials Science and Engineering, Zhengzhou University Zhengzhou, Henan 450001, China
| | - Yuping Gong
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ying Wang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Runying Guo
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences at Zhengzhou University, Zhengzhou, China
| | - Xue Zhang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yiming Liu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hongyan Mi
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Meiyue Wang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mengzhe Liu
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Rui Li
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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5
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A modified glass ionomer cement to mediate dentine repair. Dent Mater 2021; 37:1307-1315. [PMID: 34175133 DOI: 10.1016/j.dental.2021.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 05/07/2021] [Accepted: 05/25/2021] [Indexed: 11/20/2022]
Abstract
OBJECTIVES Glass ionomer cements (GIC) can be used to protect dentine following caries removal. However, GIC have little biological activity on biological repair processes, which means that neo-dentine formation remains reliant on limited endogenous regenerative processes. Wnt/β-catenin signalling is known to play a central role in stimulating tertiary dentine formation following tooth damage and can be stimulated by a range of glycogen synthase kinase (GSK3) antagonists, including lithium ions. METHODS Here, we created lithium-containing bioactive glass (BG) by substituting lithium for sodium ions in 45S5 BG. We then replaced between 10 and 40% of the powder phase of a commercial GIC with the lithium-substituted BG to create a range of formulations of 'LithGlassGIC'. In vitro physical properties of the resulting glasses were characterised and their ability to stimulate reactionary dentine formation in mouse molars in vivo was tested. RESULTS Lithium release from LithGlassGIC increased with increasing lithium content in the cement. In common with unmodified commercial GIC, all formations of LithGlassGIC showed in vitro toxicity when measured using an indirect cell culture assay based on ISO10993:5, precluding direct pulp contact. However, in a murine non-exposed pulp model of tooth damage, LithGlassGIC quickly released lithium ions, which could be transiently detected in the saliva and blood. LithGlassGIC also enhanced the formation of tertiary dentine, resulting in a thickening of the dentine at the damage site that restored lost dentine volume. Dentine regeneration was likely mediated by upregulation of Wnt/β-catenin activity, as LithGlassGIC placed in TCF/Lef:H2B-GFP reporter mice showed enhanced GFP activity. SIGNIFICANCE We conclude that LithGlassGIC acts as a biological restorative material that promotes tertiary dentine formation and restores tooth structure.
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6
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Soto J, Ding X, Wang A, Li S. Neural crest-like stem cells for tissue regeneration. Stem Cells Transl Med 2021; 10:681-693. [PMID: 33533168 PMCID: PMC8046096 DOI: 10.1002/sctm.20-0361] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 12/18/2020] [Accepted: 12/24/2020] [Indexed: 12/13/2022] Open
Abstract
Neural crest stem cells (NCSCs) are a transient population of cells that arise during early vertebrate development and harbor stem cell properties, such as self‐renewal and multipotency. These cells form at the interface of non‐neuronal ectoderm and neural tube and undergo extensive migration whereupon they contribute to a diverse array of cell and tissue derivatives, ranging from craniofacial tissues to cells of the peripheral nervous system. Neural crest‐like stem cells (NCLSCs) can be derived from pluripotent stem cells, placental tissues, adult tissues, and somatic cell reprogramming. NCLSCs have a differentiation capability similar to NCSCs, and possess great potential for regenerative medicine applications. In this review, we present recent developments on the various approaches to derive NCLSCs and the therapeutic application of these cells for tissue regeneration.
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Affiliation(s)
- Jennifer Soto
- Department of Bioengineering, University of California Los Angeles, Los Angeles, California, USA
| | - Xili Ding
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, People's Republic of China
| | - Aijun Wang
- Department of Surgery, School of Medicine, University of California Davis, Sacramento, California, USA.,Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, California, USA.,Department of Biomedical Engineering, University of California Davis, Davis, California, USA
| | - Song Li
- Department of Bioengineering, University of California Los Angeles, Los Angeles, California, USA.,Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
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Oh HA, Kwak J, Kim BJ, Jin HJ, Park WS, Choi SJ, Oh W, Um S. Migration Inhibitory Factor in Conditioned Medium from Human Umbilical Cord Blood-Derived Mesenchymal Stromal Cells Stimulates Hair Growth. Cells 2020; 9:E1344. [PMID: 32481584 PMCID: PMC7349163 DOI: 10.3390/cells9061344] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/26/2020] [Accepted: 05/27/2020] [Indexed: 12/26/2022] Open
Abstract
Conventional therapeutic applications of mesenchymal stromal cells (MSCs) focus on cell replacement and differentiation; however, increasing evidence suggests that most of their therapeutic effects are carried out by their various secretions. This study investigated the application of conditioned medium (CM) from human umbilical cord blood-derived MSCs (hUCB-MSCs) to improve hair growth and developed a method to reliably produce this optimized CM. Primed MSC-derived CM (P-CM) with combinations of TGF-β1 and LiCl was optimized by comparing its effects on the cell viability of dermal papilla cells (DPCs). P-CM significantly increased the viability of DPCs compared to CM. The secretion of vascular endothelial growth factor (VEGF) in DPCs was regulated by the macrophage migration inhibitory factor (MIF) in the P-CM secreted by MSCs. These findings suggest that P-CM can improve the efficacy in hair growth via a paracrine mechanism and that MIF in P-CM exerts hair growth-promoting effects via a VEGF-related β-catenin and p-GSK-3β [SER9] signaling pathway. Furthermore, clinical trials have shown that 5% P-CM improved androgenetic alopecia through producing an increased hair density, thickness, and growth rate, suggesting that this topical agent may be a novel and effective treatment option for patients with androgenetic alopecia.
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Affiliation(s)
- Hyun Ah Oh
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; (H.A.O.); (J.K.); (H.J.J.); (S.J.C.); (W.O.)
| | - Jihye Kwak
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; (H.A.O.); (J.K.); (H.J.J.); (S.J.C.); (W.O.)
| | - Beom Joon Kim
- Department of Dermatology, Chung-Ang University College of Medicine, Seoul 06974, Korea;
| | - Hye Jin Jin
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; (H.A.O.); (J.K.); (H.J.J.); (S.J.C.); (W.O.)
| | - Won Seok Park
- Aesthetic Research Team, Amore Pacific Corporation Research and Development Center, Yongin 17074, Korea;
| | - Soo Jin Choi
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; (H.A.O.); (J.K.); (H.J.J.); (S.J.C.); (W.O.)
| | - Wonil Oh
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; (H.A.O.); (J.K.); (H.J.J.); (S.J.C.); (W.O.)
| | - Soyoun Um
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; (H.A.O.); (J.K.); (H.J.J.); (S.J.C.); (W.O.)
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8
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Cerrizuela S, Vega-Lopez GA, Aybar MJ. The role of teratogens in neural crest development. Birth Defects Res 2020; 112:584-632. [PMID: 31926062 DOI: 10.1002/bdr2.1644] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 12/11/2019] [Accepted: 12/22/2019] [Indexed: 12/13/2022]
Abstract
The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies. Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.
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Affiliation(s)
- Santiago Cerrizuela
- Área Biología Experimental, Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT), Tucumán, Argentina.,Instituto de Biología "Dr. Francisco D. Barbieri", Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Guillermo A Vega-Lopez
- Área Biología Experimental, Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT), Tucumán, Argentina.,Instituto de Biología "Dr. Francisco D. Barbieri", Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Manuel J Aybar
- Área Biología Experimental, Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT), Tucumán, Argentina.,Instituto de Biología "Dr. Francisco D. Barbieri", Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina
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9
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Li P, Wang Y, Liu X, Zhou Z, Wang J, Zhou H, Zheng L, Yang L. Atypical antipsychotics induce human osteoblasts apoptosis via Wnt/β-catenin signaling. BMC Pharmacol Toxicol 2019; 20:10. [PMID: 30755277 PMCID: PMC6373048 DOI: 10.1186/s40360-019-0287-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Accepted: 01/22/2019] [Indexed: 01/13/2023] Open
Abstract
Background There is evidence that atypical antipsychotics (APs) increase risk of osteoporosis in schizophrenia patients, however the mechanism is unclear. The aim of the study was to explore the molecular mechanisms about Wnt/β-catenin signal pathway underlying the osteal side effects of APs. Methods We cultured human osteoblast cell line hFob1. 19 (OB) treatments with olanzapine, risperidone, amisulpride, aripiprazole or resveratrol in vitro. OB cells viability was detected by cell viability assay. OB cells apoptosis was analyzed by flow cytometry (FCM). Further apoptosis-related marker and β-catenin expression was analyzed by Western blot and Immunofluorescence analysis. Results Compared with the control group, proliferation of OB cells decreased and apoptosis rates of OB cells increased significantly in APs group (p < 0.05). There were a reduced level of Bcl-2, Mcl-1 (antiapoptotic marker) and an elevated level of Bax, Cleaved-Caspase3 (proapoptotic marker) in APs group (p < 0.05). Simultaneously, β-catenin expression decreased in cytoplasm and nucleus (p < 0.05). Compared with the just APs group, the apoptosis rates decreased and β-catenin expression increased significantly in resevratrol combined with APs group (p < 0.05). Correlation analysis showed positive correlation between β-catenin expression and the apoptotic rate in OB cells (r = − 0.515, p < 0.05). Conclusions APs cause OB cells apoptosis relating to Wnt/β-catenin signaling while resevratrol could reverse this phenomenon. Our study could lay the foundation for overcoming the APs-induced osteal side effects to improve the life quality of schizophrenia patients.
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Affiliation(s)
- Peifan Li
- Department of Psychiatry, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Yiming Wang
- Department of Psychiatry, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China. .,Neuroelectrophysiological testing center, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China. .,Undergraduate mental health education and counseling center, Guizhou Medical University, Guiyang, 550004, Guizhou, China.
| | - Xingde Liu
- Department of Cardiology, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China.
| | - Zhen Zhou
- Clinical research center, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Jun Wang
- Clinical research center, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Haiyan Zhou
- Clinical research center, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Lei Zheng
- Department of Psychiatry, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Lixia Yang
- Department of Psychiatry, Hospital Affiliated to Guizhou Medical University, Guiyang, 550004, Guizhou, China
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10
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da Silva JG, Babb R, Salzlechner C, Sharpe PT, Brauer DS, Gentleman E. Optimisation of lithium-substituted bioactive glasses to tailor cell response for hard tissue repair. JOURNAL OF MATERIALS SCIENCE 2017; 52:8832-8844. [PMID: 29056759 PMCID: PMC5644509 DOI: 10.1007/s10853-017-0838-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 01/24/2017] [Indexed: 06/07/2023]
Abstract
Bioactive glasses (BG) are used clinically because they can both bond to hard tissue and release therapeutic ions that can stimulate nearby cells. Lithium has been shown to regulate the Wnt/β-catenin cell signalling pathway, which plays important roles in the formation and repair of bone and teeth. Lithium-releasing BG, therefore, have the potential to locally regulate hard tissue formation; however, their design must be tailored to induce an appropriate biological response. Here, we optimised the release of lithium from lithium-substituted BG by varying BG composition, particle size and concentration to minimise toxicity and maximise upregulation of the Wnt target gene Axin2 in in vitro cell cultures. Our results show that we can tailor lithium release from BG over a wide therapeutic and non-toxic range. Increasing the concentration of BG in cell culture medium can induce toxicity, likely due to modulations in pH. Nevertheless, at sub-toxic concentrations, lithium released from BG can upregulate the Wnt pathway in 17IA4 cells, similarly to treatment with LiCl. Taken together, these data demonstrate that ion release from lithium-substituted BG can be tailored to maximise biological response. These data may be important in the design of BG that can regulate the Wnt/β-catenin pathway to promote hard tissue repair or regeneration.
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Affiliation(s)
- Jeison Gabriel da Silva
- Craniofacial Development and Stem Cell Biology, King’s College London, 27th Floor, Guy’s Hospital, London, SE1 9RT UK
| | - Rebecca Babb
- Craniofacial Development and Stem Cell Biology, King’s College London, 27th Floor, Guy’s Hospital, London, SE1 9RT UK
| | - Christoph Salzlechner
- Craniofacial Development and Stem Cell Biology, King’s College London, 27th Floor, Guy’s Hospital, London, SE1 9RT UK
| | - Paul T. Sharpe
- Craniofacial Development and Stem Cell Biology, King’s College London, 27th Floor, Guy’s Hospital, London, SE1 9RT UK
| | - Delia S. Brauer
- Otto Schott Institute of Materials Research, Friedrich Schiller University Jena, 07743 Jena, Germany
| | - Eileen Gentleman
- Craniofacial Development and Stem Cell Biology, King’s College London, 27th Floor, Guy’s Hospital, London, SE1 9RT UK
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11
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Qi L, Tang Y, He W, Pan H, Jiang W, Wang L, Deng W. Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson's disease model. Cytotechnology 2017; 69:277-287. [PMID: 28120140 DOI: 10.1007/s10616-016-0056-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 12/16/2016] [Indexed: 01/17/2023] Open
Abstract
Parkinson's disease (PD) is one of the most common neural degenerative disease, affecting millions of people globally. Great progress has been made in the PD treatment, and one of the most promising one is the stem cell-based therapy. Thus, studies on the differentiation of neural stem cells (NSCs) are important to the advancement in PD therapy. In this study, we used the rat NSCs to elucidate the role of Lithium in the proliferation and differentiation of NSCs by immunostaining against Ki67 and BrdU analysis as well as immunostaining against specific neuronal markers. We concluded that lithium chloride (LiCl) treatment could enhance the proliferation in NSCs and promote the dopaminergic neuronal differentiation of NSCs in vitro. This process was potentially mediated by Wnt signaling pathway. Using the 6-OHDA-induced PD models, we provided evidence to show that LiCl had the capacity to enhance the proliferation in NSCs and differentiation towards dopaminergic neurons in vivo. The beneficial effect of LiCl treatment was further validated by the fact that the motor function as well as learning and memory was improved in the PD models through Rotarod test and Morris water maze analysis. The learning and memory improvement was further supported by the increase in dendrite spine density in PD models receiving LiCl-treated NSCs. Through this study, we concluded that Lithium plays an important role in promoting NSCs' neuronal differentiation in vitro and improving the symptoms of PD models in vivo. It is of great significance that this work showed the potential application of Lithium in the PD therapy in the future.
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Affiliation(s)
- Li Qi
- Department of Neurology, The 181st Center Hospital of the People's Liberation Army, No. 1 Xin Qiao Yuan Rd., Guilin, 541002, Guangxi, China.
| | - Yonggang Tang
- Department of Neurology, The 181st Center Hospital of the People's Liberation Army, No. 1 Xin Qiao Yuan Rd., Guilin, 541002, Guangxi, China
| | - Wei He
- Department of Neurology, The 181st Center Hospital of the People's Liberation Army, No. 1 Xin Qiao Yuan Rd., Guilin, 541002, Guangxi, China
| | - Honghua Pan
- Department of Neurology, The 181st Center Hospital of the People's Liberation Army, No. 1 Xin Qiao Yuan Rd., Guilin, 541002, Guangxi, China
| | - Wenxian Jiang
- Department of Neurology, The 181st Center Hospital of the People's Liberation Army, No. 1 Xin Qiao Yuan Rd., Guilin, 541002, Guangxi, China
| | - Lin Wang
- Department of Neurology, The 181st Center Hospital of the People's Liberation Army, No. 1 Xin Qiao Yuan Rd., Guilin, 541002, Guangxi, China
| | - Weilin Deng
- Department of Neurology, The 181st Center Hospital of the People's Liberation Army, No. 1 Xin Qiao Yuan Rd., Guilin, 541002, Guangxi, China
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He XQ, Song YQ, Liu R, Liu Y, Zhang F, Zhang Z, Shen YT, Xu L, Chen MH, Wang YL, Xu BH, Yang XJ, Wang HL. Axin-1 Regulates Meiotic Spindle Organization in Mouse Oocytes. PLoS One 2016; 11:e0157197. [PMID: 27284927 PMCID: PMC4902301 DOI: 10.1371/journal.pone.0157197] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 05/25/2016] [Indexed: 11/23/2022] Open
Abstract
Axin-1, a negative regulator of Wnt signaling, is a versatile scaffold protein involved in centrosome separation and spindle assembly in mitosis, but its function in mammalian oogenesis remains unknown. Here we examined the localization and function of Axin-1 during meiotic maturation in mouse oocytes. Immunofluorescence analysis showed that Axin-1 was localized around the spindle. Knockdown of the Axin1 gene by microinjection of specific short interfering (si)RNA into the oocyte cytoplasm resulted in severely defective spindles, misaligned chromosomes, failure of first polar body (PB1) extrusion, and impaired pronuclear formation. However, supplementing the culture medium with the Wnt pathway activator LiCl improved spindle morphology and pronuclear formation. Downregulation of Axin1 gene expression also impaired the spindle pole localization of γ-tubulin/Nek9 and resulted in retention of the spindle assembly checkpoint protein BubR1 at kinetochores after 8.5 h of culture. Our results suggest that Axin-1 is critical for spindle organization and cell cycle progression during meiotic maturation in mouse oocytes.
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Affiliation(s)
- Xiao-Qin He
- Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, P. R. China
- Department of Gynaecology and Obstetrics, Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, P. R. China
- The Fifth Hospital of Wuhan, Wuhan City, Hubei Province, P. R. China
| | - Yue-Qiang Song
- New England Fertility Institute, Stamford, CT, United States of America
| | - Rui Liu
- Department of Gynaecology and Obstetrics, Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, P. R. China
| | - Yu Liu
- Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, P. R. China
| | - Fei Zhang
- Department of Gynaecology and Obstetrics, Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, P. R. China
| | - Zhen Zhang
- Xiamen Institute for Food and Drug Quality Control, Xiamen City, Fujian Province, P. R. China
| | - Yu-Ting Shen
- Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai City, P. R. China
| | - Lin Xu
- New England Fertility Institute, Stamford, CT, United States of America
| | - Ming-Huang Chen
- Department of Gynaecology and Obstetrics, Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, P. R. China
| | - Ya-Long Wang
- Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, P. R. China
| | - Bai-Hui Xu
- Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, P. R. China
| | - Xiang-Jun Yang
- Department of Gynaecology and Obstetrics, Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, P. R. China
- * E-mail: (HLW); (XJY)
| | - Hai-Long Wang
- Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, P. R. China
- * E-mail: (HLW); (XJY)
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Herencia C, Diaz-Tocados JM, Jurado L, Montes de Oca A, Rodríguez-Ortiz ME, Martín-Alonso C, Martínez-Moreno JM, Vergara N, Rodríguez M, Almadén Y, Muñoz-Castañeda JR. Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation. PLoS One 2016; 11:e0156788. [PMID: 27257912 PMCID: PMC4892678 DOI: 10.1371/journal.pone.0156788] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 05/19/2016] [Indexed: 11/26/2022] Open
Abstract
Introduction Periodontitis is a complex pathology characterized by the loss of alveolar bone. The causes and the mechanisms that promote this bone resorption still remain unknown. The knowledge of the critical regulators involved in the alteration of alveolar bone homeostasis is of great importance for developing molecular therapies. Procaine is an anesthetic drug with demethylant properties, mainly used by dentists in oral surgeries. The inhibitor role of Wnt signaling of procaine was described in vitro in colon cancer cells. Methods In this work we evaluated the role of procaine (1 uM) in osteo/odontogenesis of rat bone marrow mesenchymal stem cells. Similarly, the mechanisms whereby procaine achieves these effects were also studied. Results Procaine administration led to a drastic decrease of calcium content, alkaline phosphatase activity, alizarin red staining and an increase in the expression of Matrix Gla Protein. With respect to osteo/odontogenic markers, procaine decreased early and mature osteo/odontogenic markers. In parallel, procaine inhibited canonical Wnt/β-catenin pathway, observing a loss of nuclear β-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3β and an increase of phosphorylated β-catenin. The combination of osteo/odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3β, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3β and β-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed. Conclusions Our results demonstrated that procaine administration drastically reduced the mineralization and osteo/odontogenesis of bone marrow mesenchymal stem cells inhibiting Wnt/β-catenin pathway through the increase of Gsk3β expression and β-catenin phosphorylation.
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Affiliation(s)
- Carmen Herencia
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | - Juan Miguel Diaz-Tocados
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | - Lidia Jurado
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | - Addy Montes de Oca
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | | | - Carmen Martín-Alonso
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | - Julio M. Martínez-Moreno
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | - Noemi Vergara
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | - Mariano Rodríguez
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
| | - Yolanda Almadén
- Lipids and Atherosclerosis Unit, (CIBEROBN), Hosp Univ Reina Sofia, IMIBIC, REDinREN, Córdoba, Spain
| | - Juan R. Muñoz-Castañeda
- Instituto Maimónides para la Investigación Biomédica de Córdoba (IMIBIC)/Hospital Universitario Reina Sofía/Universidad de Córdoba, Serv Nefrologia, Córdoba, Spain
- * E-mail:
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