Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice.
10.1038/s41368-022-00185-1
- Author:
Yumei LAI
1
;
Wei ZHENG
2
;
Minghao QU
3
;
Christopher C XIAO
1
;
Sheng CHEN
3
;
Qing YAO
3
;
Weiyuan GONG
3
;
Chu TAO
3
;
Qinnan YAN
3
;
Peijun ZHANG
3
;
Xiaohao WU
4
;
Guozhi XIAO
5
Author Information
1. Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA.
2. Department of Orthopaedic Center, Xinjiang Production and Construction Corps Hospital, Urumqi, China.
3. Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, China.
4. Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, China. wxho0606@163.com.
5. Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen, China. xiaogz@sustech.edu.cn.
- Publication Type:Journal Article
- MeSH:
Aggrecans/metabolism*;
Animals;
Cartilage, Articular/metabolism*;
Chondrocytes/pathology*;
Cytoskeletal Proteins/metabolism*;
Mice;
Muscle Proteins/metabolism*;
Osteoarthritis/pathology*;
Temporomandibular Joint/pathology*
- From:
International Journal of Oral Science
2022;14(1):33-33
- CountryChina
- Language:English
-
Abstract:
The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
