南方科技大学知识苑(SUSTech KC): Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice

题名	Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice
作者	Qu, Minghao1 ; Chen, Mingjue1 ; Gong, Weiyuan1 ; Huo, Shaochuan 1,2; Yan, Qinnan1 ; Yao, Qing1 ; Lai, Yumei 3; Chen, Di 4; Wu, Xiaohao1 ; Xiao, Guozhi1
通讯作者	Wu, Xiaohao; Xiao, Guozhi
发表日期	2022-08-01
DOI	10.14336/AD.2022.0828
发表期刊	Aging and Disease 影响因子和分区
ISSN	2152-5250
卷号	14 期号:2
摘要	Osteoarthritis (OA) is the most common degenerative joint disease affecting the older populations globally. Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (Pip5k1c), a lipid kinase catalyzing the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), is involved in various cellular processes, such as focal adhesion (FA) formation, cell migration, and cellular signal transduction. However, whether Pip5k1c plays a role in the pathogenesis of OA remains unclear. Here we show that inducible deletion of Pip5k1c in aggrecan-expressing chondrocytes (cKO) causes multiple spontaneous OA-like lesions, including cartilage degradation, surface fissures, subchondral sclerosis, meniscus deformation, synovial hy perplasia, and osteophyte formation in aged (15-month-old) mice, but not in adult (7-month-old) mice. Pip5k1c loss promotes extracellular matrix (ECM) degradation, chondrocyte hypertrophy and apoptosis, and inhibits chondrocyte proliferation in the articular cartilage of aged mice. Pip5k1c loss dramatically downregulates the expressions of several key FA proteins, including activated integrin beta 1, talin, and vinculin, and thus impairs the chondrocyte adhesion and spreading on ECM. Collectively, these findings suggest that Pip5k1c expression in chondrocytes plays a critical role in maintaining articular cartilage homeostasis and protecting against age-related OA.
关键词	Pip5k1c osteoarthritis articular chondrocytes aging
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	第一 ; 通讯
资助项目	National Key Research and Development Program of China[2019YFA0906004] ; National Natural Science Foundation of China["81991513","81870532","82172375","82004395"] ; Guangdong Provincial Science and Technology Innovation Council[2017B030301018] ; Shenzhen Municipal Science and Technology Innovation Council[20200925150409001]
WOS研究方向	Geriatrics & Gerontology
WOS类目	Geriatrics & Gerontology
WOS记录号	WOS:000849338700001
出版者	INT SOC AGING & DISEASE
来源库	Web of Science
引用统计	被引频次[WOS]：7
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/395964
专题	南方科技大学医学院_生物化学系南方科技大学医学院
作者单位	1.Southern Univ Sci & Technol, Sch Med, Guangdong Prov Key Lab Cell Microenvironm & Dis R, Dept Biochem,Shenzhen Key Lab Cell Microenvironm, Shenzhen, Peoples R China 2.Guangzhou Univ Chinese Med, Shenzhen Hosp Futian, Shenzhen, Guangdong, Peoples R China 3.Rush Univ, Dept Orthoped Surg, Med Ctr, Chicago, IL 60612 USA 4.Chinese Acad Sci, Res Ctr Human Tissues & Organs Degenerat, Inst Adv Technol, Shenzhen, Peoples R China
第一作者单位	生物化学系; 南方科技大学医学院
通讯作者单位	生物化学系; 南方科技大学医学院
第一作者的第一单位	生物化学系; 南方科技大学医学院
推荐引用方式 GB/T 7714	Qu, Minghao,Chen, Mingjue,Gong, Weiyuan,et al. Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice[J]. Aging and Disease,2022,14(2).
APA	Qu, Minghao.,Chen, Mingjue.,Gong, Weiyuan.,Huo, Shaochuan.,Yan, Qinnan.,...&Xiao, Guozhi.(2022).Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice.Aging and Disease,14(2).
MLA	Qu, Minghao,et al."Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice".Aging and Disease 14.2(2022).