南方科技大学知识苑(SUSTech KC): KINDLIN-2 PRESERVES INTEGRITY OF THE ARTICULAR CARTILAGE TO PROTECT AGAINST OSTEOARTHRITIS

题名	KINDLIN-2 PRESERVES INTEGRITY OF THE ARTICULAR CARTILAGE TO PROTECT AGAINST OSTEOARTHRITIS
作者	Wu, X.; Cao, H.; Xiao, G.
发表日期	2021-09-01
DOI	10.1038/s43587-021-00165-w
发表期刊	OSTEOARTHRITIS AND CARTILAGE 影响因子和分区
ISSN	1063-4584
EISSN	1522-9653
卷号	29 期号:4
摘要	Osteoarthritis (OA) is an aging-related degenerative joint disease with a poorly defined mechanism. Here we report that kindlin-2 is highly expressed in articular chondrocytes and downregulated in the degenerated cartilage of aged mice and patients with OA. Kindlin-2 deletion in articular chondrocytes leads to spontaneous OA and exacerbates instability-induced OA lesions in adult mice. Kindlin-2 deficiency promotes mitochondrial oxidative stress and activates Stat3, leading to Runx2-mediated chondrocyte catabolism. Pharmacological inhibition of Stat3 activation or genetic ablation of Stat3 in chondrocytes reverses aberrant accumulation of Runx2 and extracellular-matrix-degrading enzymes and limits OA deteriorations caused by kindlin-2 deficiency. Deleting Runx2 in chondrocytes reverses structural changes and OA lesions caused by kindlin-2 deletion without downregulating p-Stat3. Intra-articular injection of AAV5-kindlin-2 decelerates progression of aging- and instability-induced knee joint OA in mice. Collectively, we identify a pathway consisting of kindlin-2, Stat3 and Runx2 in articular chondrocytes that is responsible for maintaining articular cartilage integrity and define a potential therapeutic target for OA.
相关链接	[来源记录]
收录类别	SCI ; ESCI
语种	英语
学校署名	第一
资助项目	National Key Research and Development Program of China[2019YFA0906004] ; National Natural Science Foundation of China["81991513","82022047","81630066","81870532","82972100"] ; Guangdong Provincial Science and Technology Innovation Council[2017B030301018] ; Science and Technology Innovation Commission of Shenzhen Municipal Government["JCYJ20180302174246105","JCYJ20180302174117738","KQJSCX20180319114434843"]
WOS研究方向	Orthopedics ; Rheumatology
WOS类目	Orthopedics ; Rheumatology
WOS记录号	WOS:000680843400006
出版者	ELSEVIER SCI LTD
ESI学科分类	CLINICAL MEDICINE
来源库	Web of Science
引用统计	被引频次[WOS]：33
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/242970
专题	南方科技大学南方科技大学医学院
作者单位	Southern Univ Sci & Technol, Shenzhen, Peoples R China
第一作者单位	南方科技大学
第一作者的第一单位	南方科技大学
推荐引用方式 GB/T 7714	Wu, X.,Cao, H.,Xiao, G.. KINDLIN-2 PRESERVES INTEGRITY OF THE ARTICULAR CARTILAGE TO PROTECT AGAINST OSTEOARTHRITIS[J]. OSTEOARTHRITIS AND CARTILAGE,2021,29(4).
APA	Wu, X.,Cao, H.,&Xiao, G..(2021).KINDLIN-2 PRESERVES INTEGRITY OF THE ARTICULAR CARTILAGE TO PROTECT AGAINST OSTEOARTHRITIS.OSTEOARTHRITIS AND CARTILAGE,29(4).
MLA	Wu, X.,et al."KINDLIN-2 PRESERVES INTEGRITY OF THE ARTICULAR CARTILAGE TO PROTECT AGAINST OSTEOARTHRITIS".OSTEOARTHRITIS AND CARTILAGE 29.4(2021).