Lysosomal destabilization:A missing link between pathological calcification and osteoarthritis  

作　　者：Tao Ye Chenyu Wang Jianfei Yan Zixuan Qin Wenpin Qin Yuxuan Ma Qianqian Wan Weicheng Lu Mian Zhang Franklin R.Tay Kai Jiao Lina Niu 

机构地区：[1]State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology,Department of Prosthodontics,School of Stomatology,The Fourth Military Medical University,Xi’an,Shaanxi,710032,PR China [2]Department of Stomatology,Tangdu Hospital,State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology,School of Stomatology,The Fourth Military Medical University,Xi’an,Shaanxi,710032,PR China [3]The Dental College of Georgia,Augusta University,Augusta,GA,30912,USA

出　　处：《Bioactive Materials》2024年第4期37-50,共14页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China(82001072,81870805,82170978);National Key R&D Program of China(2022YFC2405900,2022YFC2405901);the Shaanxi Key Scientific and Technological Innovation Team(2020TD-033).

摘　　要：Calcification of cartilage by hydroxyapatite is a hallmark of osteoarthritis and its deposition strongly correlates with the severity of osteoarthritis.However,no effective strategies are available to date on the prevention of hydroxyapatite deposition within the osteoarthritic cartilage and its role in the pathogenesis of this degenerative condition is still controversial.Therefore,the present work aims at uncovering the pathogenic mechanism of intra-cartilaginous hydroxyapatite in osteoarthritis and developing feasible strategies to counter its detrimental effects.With the use of in vitro and in vivo models of osteoarthritis,hydroxyapatite crystallites deposited in the cartilage are found to be phagocytized by resident chondrocytes and processed by the lysosomes of those cells.This results in lysosomal membrane permeabilization(LMP)and release of cathepsin B(CTSB)into the cytosol.The cytosolic CTSB,in turn,activates NOD-like receptor protein-3(NLRP3)inflammasomes and subsequently instigates chondrocyte pyroptosis.Inhibition of LMP and CTSB in vivo are effective in managing the progression of osteoarthritis.The present work provides a conceptual therapeutic solution for the prevention of osteoarthritis via alleviation of lysosomal destabilization.

关 键 词：OSTEOARTHRITIS Hydroxyapatite Lysosomal destabilization Chondrocyte pyroptosis Pathological calcification 

分 类 号：R68[医药卫生—骨科学] R318[医药卫生—外科学]