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Zhang Y, Chen Y, Shi Y, Hu H, Dai Z, Liu Z, Li X. A phase-transited lysozyme coating doped with strontium on titanium surface for bone repairing via enhanced osteogenesis and immunomodulatory. Front Cell Dev Biol 2025; 12:1506671. [PMID: 39834391 PMCID: PMC11743474 DOI: 10.3389/fcell.2024.1506671] [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: 10/05/2024] [Accepted: 12/04/2024] [Indexed: 01/22/2025] Open
Abstract
Introduction Titanium is currently recognized as an excellent orthopedic implant material, but it often leads to poor osseointegration of the implant, and is prone to aseptic loosening leading to implant failure. Therefore, biofunctionalization of titanium surfaces is needed to enhance their osseointegration and immunomodulation properties to reduce the risk of implant loosening. We concluded that the utilization of PTL-Sr is a direct and effective method for the fabrication of multifunctional implants. Methods In this Study, phase-transited lysozyme (PTL) is deposited onto the surface of titanium (Ti) to construct a functional coating and strontium chloride solution was utilized to produce PTL coatings with Sr2+. The characterization of the strontium-doped PTL coatings (PTL-Sr) was tested by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). A series of cell and animal experiments were conducted to investigate the biological functions of PTL-Sr coatings. Results The characterization indicates the successful preparation of PTL-Sr coatings. In vitro cellular experiments have demonstrated that it promotes M2 macrophage polarization and reduces inflammatory mediator production while promoting osteogenic differentiation of bone merrow mesenchymal stem cells (BMSCs). The in vivo subcutaneous implantation model demonstrated its good immunomodulatory and angiogenic properties. Discussion Titanium with PTL-Sr coatings promote biomineralization and immunomodulation, which is suitable for orthopedic applications. Further mechanistic exploration and studies using animal models is necessary to enhance the understanding of the clinical applicability of modified titanium.
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Affiliation(s)
- Yu Zhang
- Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yu Chen
- Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yidan Shi
- The High School Attached to Hunan NormalUniversity, Changsha, China
| | - Hongkun Hu
- Department of Orthopedic Surgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhongyu Dai
- Department of Orthopedic Surgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhichen Liu
- Department of Orthopedic Surgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Xuanan Li
- Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
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Cekuc MS, Ergul YS, Pius AK, Meagan M, Shinohara I, Murayama M, Susuki Y, Ma C, Morita M, Chow SKH, Bunnell BA, Lin H, Gao Q, Goodman SB. Metformin Modulates Cell Oxidative Stress to Mitigate Corticosteroid-Induced Suppression of Osteogenesis in a 3D Model. J Inflamm Res 2024; 17:10383-10396. [PMID: 39654863 PMCID: PMC11625639 DOI: 10.2147/jir.s498888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/26/2024] [Indexed: 12/12/2024] Open
Abstract
Background Corticosteroids provide well-established therapeutic benefits; however, they are also accompanied by adverse effects on bone. Metformin is a widely used medication for managing type 2 diabetes mellitus. Recent studies have highlighted additional therapeutic benefits of metformin, particularly concerning bone health and oxidative stress. Objective This research investigates the effects of prednisolone on cellular metabolic functions and bone formation using a 3D in vitro model. Then, we demonstrate the potential therapeutic effects of metformin on oxidative stress and the formation of calcified matrix due to corticosteroids. Methods Human mesenchymal stem cells (MSCs) and macrophages were cultured in a 3D GelMA scaffold and stimulated with prednisolone, with and without metformin. The adverse effects of prednisolone and metformin's therapeutic effect(s) were assessed by analyzing cell viability, osteogenesis markers, bone mineralization, and inflammatory markers. Oxidative stress was measured by evaluating reactive oxygen species (ROS) levels and ATP production. Results Prednisolone exhibited cytotoxic effects, reducing the viability of MSCs and macrophages. Lower osteogenesis potential was also detected in the MSC group. Metformin positively affected cell functions, including enhanced osteoblast activity and increased bone mineralization. Furthermore, metformin effectively reduced oxidative stress, as evidenced by decreased ROS levels and increased ATP production. These findings indicate that metformin protects against oxidative damage, thus supporting osteogenesis. Conclusion Metformin exhibits promising therapeutic potential beyond its role in diabetes management. The capacity to alleviate oxidative stress highlights the potential of metformin in supporting bone formation in inflammatory environments.
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Affiliation(s)
- Mehmet Sertac Cekuc
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Yasemin Sude Ergul
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Alexa K Pius
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Makarcyzk Meagan
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA
| | - Issei Shinohara
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Masatoshi Murayama
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Yosuke Susuki
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Chao Ma
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Mayu Morita
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Simon Kwoon-Ho Chow
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Bruce A Bunnell
- Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA
| | - Hang Lin
- Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA
| | - Qi Gao
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
| | - Stuart B Goodman
- Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA
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Wang K. The potential therapeutic role of curcumin in osteoporosis treatment: based on multiple signaling pathways. Front Pharmacol 2024; 15:1446536. [PMID: 39175539 PMCID: PMC11338871 DOI: 10.3389/fphar.2024.1446536] [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: 06/10/2024] [Accepted: 07/29/2024] [Indexed: 08/24/2024] Open
Abstract
Osteoporosis is a common chronic metabolic bone disease caused by disturbances in normal bone metabolism and an imbalance between osteoblasts and osteoclasts. Osteoporosis is characterized by a decrease in bone mass and bone density, leading to increased bone fragility. Osteoporosis is usually treated with medications and surgical methods, but these methods often produce certain side effects. Therefore, the use of traditional herbal ingredients for the treatment of osteoporosis has become a focus of attention and a hot topic in recent years. Curcumin, widely distributed among herbs such as turmeric, tulip, and curcuma longa, contains phenolic, terpenoid, and flavonoid components. Modern pharmacological studies have confirmed that curcumin has a variety of functions including antioxidant and anti-inflammatory properties. In addition, curcumin positively regulates the differentiation and promotes the proliferation of osteoblasts, which play a crucial role in bone formation. Multiple studies have shown that curcumin is effective in the treatment of osteoporosis as it interacts with a variety of signaling pathway targets, thereby interfering with the formation of osteoblasts and osteoclasts and regulating the development of osteoporosis. This review summarized the key signaling pathways and their mechanisms of action of curcumin in the prevention and treatment of osteoporosis and analyzed their characteristics and their relationship with osteoporosis and curcumin. This not only proves the medicinal value of curcumin as a traditional herbal ingredient but also further elucidates the molecular mechanism of curcumin's anti-osteoporosis effect, providing new perspectives for the prevention and treatment of osteoporosis through multiple pathways.
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Affiliation(s)
- Keyu Wang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China
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Liu W, Wang D, He G, Li T, Zhang X. A novel porous titanium with engineered surface for bone defect repair in load-bearing position. J Biomed Mater Res A 2024; 112:1083-1092. [PMID: 38411355 DOI: 10.1002/jbm.a.37689] [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] [Revised: 02/01/2024] [Accepted: 02/06/2024] [Indexed: 02/28/2024]
Abstract
Porous titanium exhibits low elastic modulus and porous structure is thought to be a promising implant in bone defect repair. However, the bioinert and low mechanical strength of porous titanium have limited its clinical application, especially in load-bearing bone defect repair. Our previous study has reported an infiltration casting and acid corrosion (IC-AC) method to fabricate a novel porous titanium (pTi) with 40% porosity and 0.4 mm pore diameter, which exerts mechanical property matching with cortical bone and interconnected channels. In this study, we introduced a nanoporous coating and incorporated an osteogenic element strontium (Sr) on the surface of porous titanium (named as Sr-micro arch oxidation [MAO]) to improve the osteogenic ability of the pTi by MAO. Better biocompatibility of Sr-MAO was verified by cell adhesion experiment and cell counting kit-8 (CCK-8) test. The in vitro osteogenic-related tests such as immunofluorescence staining, alkaline phosphatase staining and real-time polymerase chain reaction (RT-PCR) demonstrated better osteogenic ability of Sr-MAO. Femoral bone defect repair model was employed to evaluate the osseointegration of samples in vivo. Results of micro-CT scanning, sequential fluorochrome labeling and Van Gieson staining suggested that Sr-MAO showed better in vivo osteogenic ability than other groups. Taking results of both in vitro and in vivo experiment together, this study indicated the Sr-MAO porous titanium could be a promising implant load-bearing bone defect.
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Affiliation(s)
- Wei Liu
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dong Wang
- School of Mechanical and Electrical Engineering, Henan University of Technology, Zhengzhou, China
| | - Guo He
- State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Tingting Li
- Department of Infection Disease, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xianlong Zhang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Arya PN, Saranya I, Selvamurugan N. Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiation. World J Stem Cells 2024; 16:102-113. [PMID: 38455105 PMCID: PMC10915952 DOI: 10.4252/wjsc.v16.i2.102] [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: 10/22/2023] [Revised: 01/04/2024] [Accepted: 01/22/2024] [Indexed: 02/26/2024] Open
Abstract
Mesenchymal stem cells (MSCs) originate from many sources, including the bone marrow and adipose tissue, and differentiate into various cell types, such as osteoblasts and adipocytes. Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development. Osteogenesis is the process by which new bones are formed; it also aids in bone remodeling. Wnt/β-catenin and bone morphogenetic protein (BMP) signaling pathways are involved in many cellular processes and considered to be essential for life. Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body. Recent studies have indicated that these two signaling pathways contribute to osteogenic differentiation. Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway. Here, we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation, emphasizing the canonical pathways. This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch- and extracellular-regulated kinases in osteogenic differentiation and bone development.
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Affiliation(s)
- Pakkath Narayanan Arya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India
| | - Iyyappan Saranya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India
| | - Nagarajan Selvamurugan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India.
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Silva AV, Gomes DDS, Victor RDS, Santana LNDL, Neves GA, Menezes RR. Influence of Strontium on the Biological Behavior of Bioactive Glasses for Bone Regeneration. MATERIALS (BASEL, SWITZERLAND) 2023; 16:7654. [PMID: 38138796 PMCID: PMC10744628 DOI: 10.3390/ma16247654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/26/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023]
Abstract
Bioactive glasses (BGs) can potentially be applied in biomedicine, mainly for bone repair and replacement, given their unique ability to connect to natural bone tissue and stimulate bone regeneration. Since their discovery, several glass compositions have been developed to improve the properties and clinical abilities of traditional bioactive glass. Different inorganic ions, such as strontium (Sr2+), have been incorporated in BG due to their ability to perform therapeutic functions. Sr2+ has been gaining prominence due to its ability to stimulate osteogenesis, providing an appropriate environment to improve bone regeneration, in addition to its antibacterial potential. However, as there are still points in the literature that are not well consolidated, such as the influence of ionic concentrations and the BG production technique, this review aims to collect information on the state of the art of the biological behavior of BGs containing Sr2+. It also aims to gather data on different types of BGs doped with different concentrations of Sr2+, and to highlight the manufacturing techniques used in order to analyze the influence of the incorporation of this ion for bone regeneration purposes.
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Affiliation(s)
- Amanda Vieira Silva
- Graduate Program in Materials Science and Engineering, Federal University of Campina Grande, Campina Grande 58429-900, PB, Brazil;
- Laboratory of Materials Technology (LTM), Federal University of Campina Grande, Campina Grande 58429-900, PB, Brazil; (R.d.S.V.); (L.N.d.L.S.); (G.A.N.)
| | - Déborah dos Santos Gomes
- Laboratory of Materials Technology (LTM), Federal University of Campina Grande, Campina Grande 58429-900, PB, Brazil; (R.d.S.V.); (L.N.d.L.S.); (G.A.N.)
| | - Rayssa de Sousa Victor
- Laboratory of Materials Technology (LTM), Federal University of Campina Grande, Campina Grande 58429-900, PB, Brazil; (R.d.S.V.); (L.N.d.L.S.); (G.A.N.)
| | - Lisiane Navarro de Lima Santana
- Laboratory of Materials Technology (LTM), Federal University of Campina Grande, Campina Grande 58429-900, PB, Brazil; (R.d.S.V.); (L.N.d.L.S.); (G.A.N.)
| | - Gelmires Araújo Neves
- Laboratory of Materials Technology (LTM), Federal University of Campina Grande, Campina Grande 58429-900, PB, Brazil; (R.d.S.V.); (L.N.d.L.S.); (G.A.N.)
| | - Romualdo Rodrigues Menezes
- Laboratory of Materials Technology (LTM), Federal University of Campina Grande, Campina Grande 58429-900, PB, Brazil; (R.d.S.V.); (L.N.d.L.S.); (G.A.N.)
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Xi X, Gao Y, Wang J, Zheng N. Strontium chloride improves bone mass by affecting the gut microbiota in young male rats. Front Endocrinol (Lausanne) 2023; 14:1198475. [PMID: 37795367 PMCID: PMC10545847 DOI: 10.3389/fendo.2023.1198475] [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: 04/07/2023] [Accepted: 08/21/2023] [Indexed: 10/06/2023] Open
Abstract
Introduction Bone mass accumulated in early adulthood is an important determinant of bone mass throughout the lifespan, and inadequate bone deposition may lead to associated skeletal diseases. Recent studies suggest that gut bacteria may be potential factors in boosting bone mass. Strontium (Sr) as a key bioactive element has been shown to improve bone quality, but the precise way that maintains the equilibrium of the gut microbiome and bone health is still not well understood. Methods We explored the capacity of SrCl2 solutions of varying concentrations (0, 100, 200 and 400 mg/kg BW) on bone quality in 7-week-old male Wistar rats and attempted to elucidate the mechanism through gut microbes. Results The results showed that in a Wistar rat model under normal growth conditions, serum Ca levels increased after Sr-treatment and showed a dose-dependent increase with Sr concentration. Three-point mechanics and Micro-CT results showed that Sr exposure enhanced bone biomechanical properties and improved bone microarchitecture. In addition, the osteoblast gene markers BMP, BGP, RUNX2, OPG and ALP mRNA levels were significantly increased to varying degrees after Sr treatment, and the osteoclast markers RANKL and TRAP were accompanied by varying degrees of reduction. These experimental results show that Sr improves bones from multiple angles. Further investigation of the microbial population revealed that the composition of the gut microbiome was changed due to Sr, with the abundance of 6 of the bacteria showing a different dose dependence with Sr concentration than the control group. To investigate whether alterations in bacterial flora were responsible for the effects of Sr on bone remodeling, a further pearson correlation analysis was done, 4 types of bacteria (Ruminococcaceae_UCG-014, Lachnospiraceae_NK4A136_group, Alistipes and Weissella) were deduced to be the primary contributors to Sr-relieved bone loss. Of these, we focused our analysis on the most firmly associated Ruminococcaceae_UCG-014. Discussion To summarize, our current research explores changes in bone mass following Sr intervention in young individuals, and the connection between Sr-altered intestinal flora and potentially beneficial bacteria in the attenuation of bone loss. These discoveries underscore the importance of the "gut-bone" axis, contributing to an understanding of how Sr affects bone quality, and providing a fresh idea for bone mass accumulation in young individuals and thereby preventing disease due to acquired bone mass deficiency.
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Affiliation(s)
- Xueyao Xi
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yanan Gao
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Jiaqi Wang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Nan Zheng
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
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Skalny AV, Aschner M, Silina EV, Stupin VA, Zaitsev ON, Sotnikova TI, Tazina SI, Zhang F, Guo X, Tinkov AA. The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings. Biomolecules 2023; 13:1006. [PMID: 37371586 DOI: 10.3390/biom13061006] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/07/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
The objective of the present study was to review recent epidemiological and clinical data on the association between selected minerals and trace elements and osteoporosis, as well as to discuss the molecular mechanisms underlying these associations. We have performed a search in the PubMed-Medline and Google Scholar databases using the MeSH terms "osteoporosis", "osteogenesis", "osteoblast", "osteoclast", and "osteocyte" in association with the names of particular trace elements and minerals through 21 March 2023. The data demonstrate that physiological and nutritional levels of trace elements and minerals promote osteogenic differentiation through the up-regulation of BMP-2 and Wnt/β-catenin signaling, as well as other pathways. miRNA and epigenetic effects were also involved in the regulation of the osteogenic effects of trace minerals. The antiresorptive effect of trace elements and minerals was associated with the inhibition of osteoclastogenesis. At the same time, the effect of trace elements and minerals on bone health appeared to be dose-dependent with low doses promoting an osteogenic effect, whereas high doses exerted opposite effects which promoted bone resorption and impaired bone formation. Concomitant with the results of the laboratory studies, several clinical trials and epidemiological studies demonstrated that supplementation with Zn, Mg, F, and Sr may improve bone quality, thus inducing antiosteoporotic effects.
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Affiliation(s)
- Anatoly V Skalny
- Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, 150003 Yaroslavl, Russia
- Center of Bioelementology and Human Ecology, Institute of Biodesign and Modeling of Complex Systems, Department of Therapy of the Institute of Postgraduate Education, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Ekaterina V Silina
- Center of Bioelementology and Human Ecology, Institute of Biodesign and Modeling of Complex Systems, Department of Therapy of the Institute of Postgraduate Education, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
| | - Victor A Stupin
- Department of Hospital Surgery No. 1, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
| | - Oleg N Zaitsev
- Department of Physical Education, Yaroslavl State Technical University, 150023 Yaroslavl, Russia
| | - Tatiana I Sotnikova
- Center of Bioelementology and Human Ecology, Institute of Biodesign and Modeling of Complex Systems, Department of Therapy of the Institute of Postgraduate Education, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
- City Clinical Hospital n. a. S.P. Botkin of the Moscow City Health Department, 125284 Moscow, Russia
| | - Serafima Ia Tazina
- Center of Bioelementology and Human Ecology, Institute of Biodesign and Modeling of Complex Systems, Department of Therapy of the Institute of Postgraduate Education, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
| | - Feng Zhang
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Health Science Center, School of Public Health, Xi'an Jiaotong University, Xi'an 710061, China
| | - Xiong Guo
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Health Science Center, School of Public Health, Xi'an Jiaotong University, Xi'an 710061, China
| | - Alexey A Tinkov
- Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, 150003 Yaroslavl, Russia
- Center of Bioelementology and Human Ecology, Institute of Biodesign and Modeling of Complex Systems, Department of Therapy of the Institute of Postgraduate Education, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
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Sheng X, Li C, Wang Z, Xu Y, Sun Y, Zhang W, Liu H, Wang J. Advanced applications of strontium-containing biomaterials in bone tissue engineering. Mater Today Bio 2023; 20:100636. [PMID: 37441138 PMCID: PMC10333686 DOI: 10.1016/j.mtbio.2023.100636] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 04/04/2023] [Accepted: 04/14/2023] [Indexed: 07/15/2023] Open
Abstract
Strontium (Sr) and strontium ranelate (SR) are commonly used therapeutic drugs for patients suffering from osteoporosis. Researches have showed that Sr can significantly improve the biological activity and physicochemical properties of materials in vitro and in vivo. Therefore, a large number of strontium containing biomaterials have been developed for repairing bone defects and promoting osseointegration. In this review, we provide a comprehensive overview of Sr-containing biomaterials along with the current state of their clinical use. For this purpose, the different types of biomaterials including calcium phosphate, bioactive glass, and polymers are discussed and provided future outlook on the fabrication of the next-generation multifunctional and smart biomaterials.
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Affiliation(s)
| | | | - Zhonghan Wang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
| | - Yu Xu
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
| | - Yang Sun
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
| | - Weimin Zhang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
| | - He Liu
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
| | - Jincheng Wang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun, 130041, Jilin, China
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You J, Zhang Y, Zhou Y. Strontium Functionalized in Biomaterials for Bone Tissue Engineering: A Prominent Role in Osteoimmunomodulation. Front Bioeng Biotechnol 2022; 10:928799. [PMID: 35875505 PMCID: PMC9298737 DOI: 10.3389/fbioe.2022.928799] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 06/13/2022] [Indexed: 12/24/2022] Open
Abstract
With the development of bone tissue engineering bio-scaffold materials by adding metallic ions to improve bone healing have been extensively explored in the past decades. Strontium a non-radioactive element, as an essential osteophilic trace element for the human body, has received widespread attention in the medical field due to its superior biological properties of inhibiting bone resorption and promoting osteogenesis. As the concept of osteoimmunology developed, the design of orthopedic biomaterials has gradually shifted from “immune-friendly” to “immunomodulatory” with the aim of promoting bone healing by modulating the immune microenvironment through implanted biomaterials. The process of bone healing can be regarded as an immune-induced procedure in which immune cells can target the effector cells such as macrophages, neutrophils, osteocytes, and osteoprogenitor cells through paracrine mechanisms, affecting pathological alveolar bone resorption and physiological bone regeneration. As a kind of crucial immune cell, macrophages play a critical role in the early period of wound repair and host defense after biomaterial implantation. Despite Sr-doped biomaterials being increasingly investigated, how extracellular Sr2+ guides the organism toward favorable osteogenesis by modulating macrophages in the bone tissue microenvironment has rarely been studied. This review focuses on recent knowledge that the trace element Sr regulates bone regeneration mechanisms through the regulation of macrophage polarization, which is significant for the future development of Sr-doped bone repair materials. We will also summarize the primary mechanism of Sr2+ in bone, including calcium-sensing receptor (CaSR) and osteogenesis-related signaling pathways.
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Affiliation(s)
- Jiaqian You
- Department of Oral Implantology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, China
| | - Yidi Zhang
- Department of Oral Implantology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, China
| | - Yanmin Zhou
- Department of Oral Implantology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, China
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Mengdi Z, Jiayi L, Canfeng L, Guofeng W, Yutong W, Pengzhou H, Yikun Z, Xintao Z, Bin T. Surface modification of polyetheretherketone (PEEK) to enhance osteointegration by grafting strontium Eucommia ulmoides polysaccharides. Int J Biol Macromol 2022; 211:230-237. [PMID: 35561859 DOI: 10.1016/j.ijbiomac.2022.05.048] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 12/17/2022]
Abstract
The complex bone regeneration microenvironment puts high demands on orthopedic implants. The implants are not only desired to satisfy the meeting of the biomechanical properties, but should also possess capabilities to promote osseointegration and bone immune regulation. PEEK is a promising polymeric material for bone implants due to its suitable mechanical properties that well match natural cortical bone tissue. However, its inert biological properties limit its application. As a newly-developed bioactive polysaccharides complex, strontium Eucommia ulmoides polysaccharides (EUP-Sr) has been proved to have capabilities including promoting osteogenesis and regulating bone immunity. In this study, in order to improve the bioactivities of PEEK, we introduce EUP-Sr to the PEEK surface via polydopamine-based coating and form a bioactive PEEK named DPEEK@EUP-Sr. The as-fabricated DPEEK@EUP-Sr was systematically investigated through scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle analysis to verify the successful introduction of EUP-Sr to PEEK, and in vitro biological experiments including cell proliferation and RT-PCR analysis suggested that the DPEEK@EUP-Sr can effectively promote the proliferation of preosteoblast MC3T3-E1, and exhibit significant anti-inflammation and osteogenesis effects, and so should be beneficial for osteointegration between bone and implants.
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Affiliation(s)
- Zhang Mengdi
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen, Shenzhen, Guangdong, PR China
| | - Liu Jiayi
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China
| | - Li Canfeng
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen, Shenzhen, Guangdong, PR China
| | - Wu Guofeng
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China
| | - Wu Yutong
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China
| | - Huang Pengzhou
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen, Shenzhen, Guangdong, PR China
| | - Zhao Yikun
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen, Shenzhen, Guangdong, PR China
| | - Zhang Xintao
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen, Shenzhen, Guangdong, PR China.
| | - Tang Bin
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, PR China; Shenzhen Key Laboratory of Cell Microenvironment, PR China Hospital, Shenzhen, Guangdong, PR China.
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12
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[Knockdown of long non-coding RNA MIR4697 host gene inhibits adipogenic differentiation in bone marrow mesenchymal stem cells]. BEIJING DA XUE XUE BAO. YI XUE BAN = JOURNAL OF PEKING UNIVERSITY. HEALTH SCIENCES 2022; 54. [PMID: 35435199 PMCID: PMC9069036 DOI: 10.19723/j.issn.1671-167x.2022.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To preliminarily investigate the role of long non-coding RNA (lncRNA) MIR4697 host gene (MIR4697HG) in regulating the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS For adipogenic differentiation, BMSCs were induced in adipogenic media for 10 days. The mRNA expression levels of lncRNA MIR4697HG and adipogenic marker genes including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhanced binding protein α (CEBP/α) and adiponectin (ADIPQ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) at different time points (0, 1, 2, 3, 5, 7, 10 days). The MIR4697HG stable knockdown-BMSC cell line was generated by infection of MIR4697HG shRNA-containing lentiviruses. To avoid off-target effect, two target sequences (shMIR4697HG-1, shMIR4697HG-2) were designed. And then cells were induced to differentiate in adipogenic medium. Oil red O staining, Western blot and qRT-PCR were used to detect the effect of MIR4697HG knockdown on adipogenic differentiation of BMSCs. RESULTS The mRNA expression level of MIR4697HG was significantly increased during adipogenic differentiation (P < 0.01), and adipogenic differentiation of BMSCs was evidenced by upregulated mRNA levels of specific adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ. Observed by fluorescence microscopy, more than 90% transfected target cells expressed green fluorescent protein successfully after shMIR4697HG-1 group, shMIR4697HG-2 group and shNC group transfection for 72 h. And the transfection efficiency of MIR4697HG examined by qRT-PCR was above 60%. Then the BMSCs were treated with adipogenic media for 7 days and showed that the mRNA expression levels of adipogenesis-related genes including PPARγ, CEBP/α and ADIPQ were significantly decreased in the MIR4697HG knockdown group (P < 0.01), while the expression levels of PPARγ and CEBP/α proteins were decreased remarkably as well (P < 0.01). Consistently, MIR4697HG knockdown BMSCs formed less lipid droplets compared with the control BMSCs, which further demonstrated that MIR4697HG knockdown inhibited adipogenic differentiation of BMSCs. CONCLUSION lncRNA MIR4697HG played a crucial role in regulating the adipogenic differentiation of BMSCs, and MIR4697HG knockdown significantly inhibited the adipogenic differentiation of BMSCs. These data may suggest that lncRNA MIR4697HG could serve as a therapeutic potential target for the aberrant adipogenic differentiation-associated disorders including osteoporosis.
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Ataie M, Nourmohammadi J, Seyedjafari E. Carboxymethyl carrageenan immobilized on 3D-printed polycaprolactone scaffold for the adsorption of calcium phosphate/strontium phosphate adapted to bone regeneration. Int J Biol Macromol 2022; 206:861-874. [PMID: 35314263 DOI: 10.1016/j.ijbiomac.2022.03.096] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 02/26/2022] [Accepted: 03/15/2022] [Indexed: 11/28/2022]
Abstract
Three dimensional (3D) substrates based on natural and synthetic polymers enhance the osteogenic and mechanical properties of the bone tissue engineering scaffolds. Here, a novel bioactive composite scaffolds from polycaprolactone /kappa-carrageenan were developed for bone regeneration applications. 3D PCL scaffolds were fabricated by 3D printing method followed by coating with carboxymethyl kappa-carrageenan. This organic film was used to create calcium and strontium phosphate layers via a modified alternate soaking process in CaCl 2 /SrCl 2 and Na2HPO4 solutions in which calcium ions were replaced by strontium, with different amounts of strontium in the solutions. Various characterization techniques were executed to analyze the effects of strontium ion on the scaffold properties. The morphological results demonstrated the highly porous with interconnected pores and uniform pore sizes scaffolds. It was indicated that the highest crystallinity and compressive strength were obtained when 100% CaCl2 was replaced by SrCl2 in the solution (P-C-Sr). Incorporation of Sr onto the structure increased the degradation rate of the scaffolds. Mesenchymal stem cells (MSCs) culture on the scaffolds showed that Sr effectively improved attachment and viability of the MSCs and accelerated osteogenic differentiation as revealed by Alkaline phosphatase activity, calcium content and Real Time-Reverse transcription polymerase chain reaction assays.
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Affiliation(s)
- Maryam Ataie
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
| | - Jhamak Nourmohammadi
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran.
| | - Ehsan Seyedjafari
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
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The Effect of Strontium-Substituted Hydroxyapatite Nanofibrous Matrix on Osteoblast Proliferation and Differentiation. MEMBRANES 2021; 11:membranes11080624. [PMID: 34436387 PMCID: PMC8401295 DOI: 10.3390/membranes11080624] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 11/20/2022]
Abstract
Natural bone tissue consists primarily of bioapatite and collagen. Synthetic hydroxyapatite (HA) possesses good biocompatibility, bioactivity, and osteoconductivity due to its chemical and biological similarity to bioapatite. Hence, HA has been widely used as a bone graft, cell carrier and drug/gene delivery carrier. Moreover, strontium-substituted hydroxyapatite (SrHA) can enhance osteogenic differentiation and inhibit adipogenic differentiation of mesenchymal stem cells. Hence, SrHA has the potential to be used as a bone graft for bone regeneration. It is widely accepted that cell adhesion and most cellular activities are sensitive to the topography and molecular composition of the matrix. Electrospun polymer or polymer-bioceramic composite nanofibers have been demonstrated to enhance osteoblast differentiation. However, to date, no studies have investigated the effect of nanofibrous bioceramic matrices on osteoblasts. In this study, hydroxyapatite nanofiber (HANF) and strontium-substituted hydroxyapatite nanofiber (SrHANF) matrices were fabricated by electrospinning. The effect of the HANF components on MG63 osteoblast-like cells was evaluated by cell morphology, proliferation, alkaline phosphatase activity (ALP) and gene expression levels of RUNX2, COLI, OCN and BSP. The results showed that MG63 osteoblast-like cells exhibited higher ALP and gene expression levels of RUNX2, COLI, BSP and OCN on the SrHANF matrix than the HANF matrix. Hence, SrHANFs could enhance the differentiation of MG63 osteoblast-like cells.
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Xu AT, Xie YW, Xu JG, Li J, Wang H, He FM. Effects of strontium-incorporated micro/nano rough titanium surfaces on osseointegration via modulating polarization of macrophages. Colloids Surf B Biointerfaces 2021; 207:111992. [PMID: 34391168 DOI: 10.1016/j.colsurfb.2021.111992] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 07/13/2021] [Accepted: 07/18/2021] [Indexed: 11/25/2022]
Abstract
Macrophages perform multiple functions in both inflammation and wound healing, and are one of the fore front cells during implant osseointegration that influence subsequent process. Essential trace element modification may effectively modulate titanium implant surface biological properties. In this work, strontium (Sr) incorporated micro/nano rough titanium surfaces (Sr-SLA) was fabricated by hydrothermal treatment, and immunoreaction of macrophages was further investigated. In vitro results revealed that Sr doping inhibited inflammatory response of macrophages, further attenuated the inhibitory effect on following bone marrow derived cells (BMSCs) osteogenic differentiation. The regulation of macrophages by Sr-SLA likely involved ERK signaling pathway. Consistently, the in vivo study showed that compared with titanium surface sand-blasted with large grit and double acid-etched (SLA) implants, Sr-SLA implants could enhance new bone formation accompanied with more alternatively activated M2 macrophages infiltration and less classically activated M1 macrophages infiltration. These results reveal the immunomodulatory ability of Sr-SLA of adjusting the functional status of macrophages through inhibiting M1 polarization while promoting M2 polarization.
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Affiliation(s)
- An-Tian Xu
- Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Yi-Wen Xie
- Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Jian-Gang Xu
- Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Jia Li
- Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Hui Wang
- Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China
| | - Fu-Ming He
- Department of Prosthodontics, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006, China.
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Ahmed RY, Elsherbini AM, Elkhier MTA, Soussa EF. A comparison of the early therapeutic effects of allogeneic bone marrow-derived mesenchymal stem cells and calcitonin on the healing of surgically induced mandibular bone defects in osteoporotic rats. Arch Oral Biol 2020; 120:104934. [PMID: 33091660 DOI: 10.1016/j.archoralbio.2020.104934] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 09/25/2020] [Accepted: 09/26/2020] [Indexed: 11/18/2022]
Abstract
OBJECTIVES This study aimed to evaluate and compare the early biological effects of allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) versus salmon calcitonin (SC) on healing of surgically induced mandibular bone defects in osteoporotic rats. METHODS Sixty-one female albino rats were included in this study, four of them were used for BMSCs isolation. The remaining 57 rats were divided into 4 groups. Group I (negative control), 12 rats received a vehicle injection after which a unilateral mandibular defect was created in each rat. Osteoporosis was induced in the remaining 45 rats then rats were randomly allocated into 3 equal groups (15 each). Surgical defects were created as in group I. The defects were left to heal spontaneously in group II; positive control. While in group III each defect was filled with an absorbable hemostatic gelatin sponge loaded by 10 IU of injectable SC and in group IV the sponge was seeded by 0.5 × 106 BMSCs. Rats were euthanized at 1st, 2nd, and 4th week postsurgically. Hematoxylin and eosin, Masson's trichrome, picrosirius, and alizarin red s stains were used, followed by statistical analysis. RESULTS BMSCs-treatment showed marked enhanced bone healing. Moreover, collagen fibers and calcium deposits area percentages were statistically significantly higher when compared to the other groups particularly at 2 and 4 weeks. CONCLUSIONS Local application of bone marrow-derived mesenchymal stem cells and salmon calcitonin may be an effective therapy for treatment of osteoporotic bone defects, with privilege to the stem cells in terms of quantity and quality of regenerated bone.
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Affiliation(s)
- Rana Y Ahmed
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
| | - Amira M Elsherbini
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt.
| | - Mazen Th Abou Elkhier
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
| | - Essam F Soussa
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
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Liu L, Zheng J, Yang Y, Ni L, Chen H, Yu D. Hesperetin alleviated glucocorticoid-induced inhibition of osteogenic differentiation of BMSCs through regulating the ERK signaling pathway. Med Mol Morphol 2020; 54:1-7. [PMID: 32253606 DOI: 10.1007/s00795-020-00251-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 03/29/2020] [Indexed: 12/11/2022]
Abstract
The objective of this study is to investigate the protective role of hesperetin for the glucocorticoid-induced osteoporosis (GIOP) and related mechanisms. In this study, we investigated the protective effects of hesperetin on dexamethasone (DEX)-induced osteogenic inhibition in bone marrow mesenchymal stem cells (BMSCs). The mineralization, real-time quantitative polymerase chain reaction assays (RT-qPCR), immunofluorescence and western blot were used to assess the protective effects of hesperetin in DEX-treated BMSCs during osteogenic differentiation. Our results showed that hesperetin promoted alkaline phosphatase (ALP) activity and the mineralization in DEX-treated BMSCs during osteogenic differentiation. The expression of osteogenic mRNA and proteins further confirmed the protective effect of hesperetin in DEX-treated BMSCs. Furthermore, hesperetin activated ERK signal pathway in DEX-treated BMSCs. ERK inhibitor U0126 could abolish the protective effect of hesperein in DEX-treated BMSCs. In conclusion, our study demonstrated that hesperetin alleviated glucocorticoid-induced inhibition of osteogenic differentiation through ERK signal pathway in BMSCs. It may be a potential therapeutic agent for protecting against glucocorticoid-induced osteoporosis.
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Affiliation(s)
- Ling Liu
- Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, Zhejiang, People's Republic of China.,Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China
| | - Jie Zheng
- Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, Zhejiang, People's Republic of China.,Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China
| | - YaZhen Yang
- Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, Zhejiang, People's Republic of China.,Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China
| | - Lingjuan Ni
- Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, Zhejiang, People's Republic of China.,Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China
| | - Hongyu Chen
- Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, Zhejiang, People's Republic of China. .,Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China.
| | - Dongrong Yu
- Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, Zhejiang, People's Republic of China. .,Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou Hospital of Traditional Chinese Medicine, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China.
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