Liu Hui1, Xuan Shoumei1, Zhang Zhoujing1, Gu Kuang1, Zou Duohong2, He Jiacai1,3, Zhou Yong4,5. 1. College and Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China. 2. Department of Oral Surgery, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, China. 3. Department of Dental Implantology, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China. 4. College and Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China. zhouyong7592@hotmail.com. 5. Department of Dental Implantology, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China. zhouyong7592@hotmail.com.
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.
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.