P M van der Kraan1, W B van den Berg. 1. Department of Rheumatology, Radboud University, Medical Centre, Geert Grooteplein 28, 6525 Nijmegen, The Netherlands. P.vanderkraan@reuma.umcn.nl
Abstract
OBJECTIVE: To review the literature on the role and regulation of chondrocyte terminal differentiation (hypertrophy-like changes) in osteoarthritis (OA) and to integrate this in a conceptual model of primary OA development. METHODS: Papers investigating chondrocyte terminal differentiation in human OA cartilage and experimental models of OA were recapitulated and discussed. Focus has been on the occurrence of hypertrophy-like changes in chondrocytes and the factors described to play a role in regulation of chondrocyte hypertrophy-like changes in OA. RESULTS: Chondrocyte hypertrophy-like changes are reported in both human OA and experimental OA models by most investigators. These changes play a crucial part in the OA disease process by protease-mediated cartilage degradation. We propose that altered chondrocyte behavior and concomitant cartilage degradation result in a disease-amplifying loop, leading to a mixture of disease stages and cellular responses within an OA joint. CONCLUSION: Chondrocyte hypertrophy-like changes play a role in early and late stage OA. Since not all cells in an OA joint are synchronized, inhibition of hypertrophy-like changes might be a therapeutic target to slow down further OA progression. Copyright Â
OBJECTIVE: To review the literature on the role and regulation of chondrocyte terminal differentiation (hypertrophy-like changes) in osteoarthritis (OA) and to integrate this in a conceptual model of primary OA development. METHODS: Papers investigating chondrocyte terminal differentiation in human OA cartilage and experimental models of OA were recapitulated and discussed. Focus has been on the occurrence of hypertrophy-like changes in chondrocytes and the factors described to play a role in regulation of chondrocyte hypertrophy-like changes in OA. RESULTS: Chondrocyte hypertrophy-like changes are reported in both human OA and experimental OA models by most investigators. These changes play a crucial part in the OA disease process by protease-mediated cartilage degradation. We propose that altered chondrocyte behavior and concomitant cartilage degradation result in a disease-amplifying loop, leading to a mixture of disease stages and cellular responses within an OA joint. CONCLUSION: Chondrocyte hypertrophy-like changes play a role in early and late stage OA. Since not all cells in an OA joint are synchronized, inhibition of hypertrophy-like changes might be a therapeutic target to slow down further OA progression. Copyright Â
Authors: Qian Wang; Kazuhiro Onuma; Changhao Liu; Heidi Wong; Michelle S Bloom; Eileen E Elliott; Richard Rl Cao; Nick Hu; Nithya Lingampalli; Orr Sharpe; Xiaoyan Zhao; Dong Hyun Sohn; Christin M Lepus; Jeremy Sokolove; Rong Mao; Cecilia T Cisar; Harini Raghu; Constance R Chu; Nicholas J Giori; Stephen B Willingham; Susan S Prohaska; Zhen Cheng; Irving L Weissman; William H Robinson Journal: JCI Insight Date: 2019-09-19