TY  - JOUR
AU  - Lai, Yumei
AU  - Zheng, Wei
AU  - Qu, Minghao
AU  - Xiao, Christopher C.
AU  - Chen, Sheng
AU  - Yao, Qing
AU  - Gong, Weiyuan
AU  - Tao, Chu
AU  - Yan, Qinnan
AU  - Zhang, Peijun
AU  - Wu, Xiaohao
AU  - Xiao, Guozhi
PY  - 2022
TI  - Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice
JO  - International Journal of Oral Science
SN  - 1674-2818
SP  - 33
VL  - 14
AB  - 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.
UR  - https://doi.org/10.1038/s41368-022-00185-1
DO  - 10.1038/s41368-022-00185-1