Hao Yu1,2, Yan Liu1,2, Xiangwen Yang1,2, Jiajing He1,2, Fan Zhang2,3, Qun Zhong1,2, Xiaojing Guo4,5. 1. Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China. 2. Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China. 3. Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China. 4. Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, China. guo_xiaojing@fudan.edu.cn. 5. Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, China. guo_xiaojing@fudan.edu.cn.
Abstract
BACKGROUND: Cartilage regeneration is a key step in functional reconstruction for temporomandibular joint osteoarthritis (TMJ-OA) but is a difficult issue to address. Strontium ranelate (SrR) is an antiosteoporosis drug that has been proven to affect OA in recent years, but its effect on chondrogenesis and the underlying mechanism are still unclear. METHODS: Bone mesenchymal stem cells (BMSCs) from Sprague-Dawley (SD) rats were induced in chondrogenic differentiation medium with or without SrR, XAV-939, and LiCl. CCK-8 assays were used to examine cell proliferation, and alcian blue staining, toluidine blue staining, immunofluorescence, and PCR analysis were performed. Western blot (WB) analyses were used to assess chondrogenic differentiation of the cells. For an in vivo study, 30 male SD rats with cartilage defects on both femoral condyles were used. The defect sites were not filled, filled with silica nanosphere plus gelatine-methacryloyl (GelMA), or filled with SrR-loaded silica nanosphere plus GelMA. After 3 months of healing, paraffin sections were made, and toluidine blue staining, safranin O/fast green staining, and immunofluorescent or immunohistochemical staining were performed for histological evaluation. The data were analyzed by SPSS 26.0 software. RESULTS: Low concentrations of SrR did not inhibit cell proliferation, and the cells treated with SrR (0.25 mmol/L) showed stronger chondrogenesis than the control. XAV-939, an inhibitor of β-catenin, significantly promoted chondrogenesis, and SrR did not suppress this effect, while LiCl, an agonist of β-catenin, strongly suppressed chondrogenesis, and SrR reversed this inhibitory effect. In vivo study showed a significantly better cartilage regeneration and a lower activation level of β-catenin by SrR-loaded GelMA than the other treatments. CONCLUSION: SrR could promote BMSCs chondrogenic differentiation by inhibiting the Wnt/β-catenin signaling pathway and accelerate cartilage regeneration in rat femoral condyle defects.
BACKGROUND: Cartilage regeneration is a key step in functional reconstruction for temporomandibular joint osteoarthritis (TMJ-OA) but is a difficult issue to address. Strontium ranelate (SrR) is an antiosteoporosis drug that has been proven to affect OA in recent years, but its effect on chondrogenesis and the underlying mechanism are still unclear. METHODS: Bone mesenchymal stem cells (BMSCs) from Sprague-Dawley (SD) rats were induced in chondrogenic differentiation medium with or without SrR, XAV-939, and LiCl. CCK-8 assays were used to examine cell proliferation, and alcian blue staining, toluidine blue staining, immunofluorescence, and PCR analysis were performed. Western blot (WB) analyses were used to assess chondrogenic differentiation of the cells. For an in vivo study, 30 male SD rats with cartilage defects on both femoral condyles were used. The defect sites were not filled, filled with silica nanosphere plus gelatine-methacryloyl (GelMA), or filled with SrR-loaded silica nanosphere plus GelMA. After 3 months of healing, paraffin sections were made, and toluidine blue staining, safranin O/fast green staining, and immunofluorescent or immunohistochemical staining were performed for histological evaluation. The data were analyzed by SPSS 26.0 software. RESULTS: Low concentrations of SrR did not inhibit cell proliferation, and the cells treated with SrR (0.25 mmol/L) showed stronger chondrogenesis than the control. XAV-939, an inhibitor of β-catenin, significantly promoted chondrogenesis, and SrR did not suppress this effect, while LiCl, an agonist of β-catenin, strongly suppressed chondrogenesis, and SrR reversed this inhibitory effect. In vivo study showed a significantly better cartilage regeneration and a lower activation level of β-catenin by SrR-loaded GelMA than the other treatments. CONCLUSION:SrR could promote BMSCs chondrogenic differentiation by inhibiting the Wnt/β-catenin signaling pathway and accelerate cartilage regeneration in ratfemoral condyle defects.
Authors: B Shoukri; J C Prieto; A Ruellas; M Yatabe; J Sugai; M Styner; H Zhu; C Huang; B Paniagua; S Aronovich; L Ashman; E Benavides; P de Dumast; N T Ribera; C Mirabel; L Michoud; Z Allohaibi; M Ioshida; L Bittencourt; L Fattori; L R Gomes; L Cevidanes Journal: J Dent Res Date: 2019-07-24 Impact factor: 6.116
Authors: Sara Tenti; Sara Cheleschi; Giacomo Maria Guidelli; Mauro Galeazzi; Antonella Fioravanti Journal: Mod Rheumatol Date: 2014-03-19 Impact factor: 3.023
Authors: Jean-Yves Reginster; Janusz Badurski; Nicholas Bellamy; William Bensen; Roland Chapurlat; Xavier Chevalier; Claus Christiansen; Harry Genant; Federico Navarro; Evgeny Nasonov; Philip N Sambrook; Timothy D Spector; Cyrus Cooper Journal: Ann Rheum Dis Date: 2012-11-01 Impact factor: 19.103