Abstract
Background:
The role of sex hormones and their receptors has drawn much attention in the process of cartilage regeneration. This study aimed to investigate the effect of androgen receptor (AR) on the chondrogenic ability of articular chondrocytes and the related mechanism.
Methods:
Articular chondrocytes were isolated, cultured, identified by toluidine blue staining and then transduced with lentivirus carrying the AR gene. The cell viability was determined using Cell Counting Kit-8, and cell apoptosis was assessed by flow cytometry analysis. The effects of AR overexpression on the expression of cartilage-specific proteins and some signalling molecules were evaluated by real-time PCR and Western blotting. Using 24 New Zealand rabbits, the regeneration of rabbit articular cartilage defects was further investigated in vivo and evaluated histologically.
Results:
The overexpression of AR significantly reduced the apoptosis rate of chondrocytes but did not affect their proliferation. The overexpression of AR also promoted the expression of Sry-related HMG box 9, collagen II and aggrecan, decreased the expression of matrix metalloproteinase-13, and downregulated p-S6 and RICTOR. The experimental group with AR-overexpressing chondrocytes exhibited superior regeneration of cartilage defects.
Conclusion:
AR overexpression can maintain the phenotype of chondrocytes and promote chondrogenesis in vitro and in vivo. mTOR-related signalling was inhibited.
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Acknowledgements
This work was supported by National Natural Science Foundation of China (31700849); the Youth Foundation of from Anhui Medical University (XJ201633) and Natural Science Foundation of Anhui Province (1708085QH184). The funders had no role in the study design, data collection or analysis, the decision to publish, or preparation of the manuscript.
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LH: experiment operation In vitro and in vivo, data analysis and interpretation, manuscript writing. XS: experiment operation In vitro and in vivo, data analysis and interpretation. ZZ: experiment operation In vitro and in vivo. GK: experiment operation in vivo. ZD: Conception and design. HJ: Conception and design. ZY: Conception and design, experiment operation in vitro and in vivo, data analysis and interpretation, manuscript writing, final approval of manuscript.
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All the experiment involving animal in this study was approved by the Medical Ethics Committee of Anhui Medical University (No. LLSC20210692) and performed under the rules of the Medical Ethics Committee of Anhui Medical University. There is no investigation involving human in this work.
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Hui, L., Shoumei, X., Zhoujing, Z. et al. Effects of Androgen Receptor Overexpression on Chondrogenic Ability of Rabbit Articular Chondrocytes. Tissue Eng Regen Med 18, 641–650 (2021). https://doi.org/10.1007/s13770-021-00358-9
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DOI: https://doi.org/10.1007/s13770-021-00358-9