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.

髁突软骨的进行性破坏是颞下颌关节 (TMJ) 骨关节炎 (OA) 的一个标志；然而，其机制尚不完全清楚。在这里，我们发现 Kindlin-2（一种关键的粘着斑蛋白）在小鼠下颌髁软骨细胞中被强烈检测到。我们发现表达聚集蛋白聚糖的髁突软骨细胞中 Kindlin-2 的基因消融会诱导多种自发性骨关节炎病变，包括进行性软骨损失和变形、表面裂隙以及 TMJ 中的异位软骨和骨形成。 Kindlin-2 缺失显着下调聚集蛋白聚糖、Col2a1 和蛋白聚糖 4 (Prg4)（所有合成代谢细胞外基质蛋白）的表达，并通过诱导髁突软骨细胞中 Runx2 和 Mmp13 的表达来促进 TMJ 软骨的分解代谢。 Kindlin-2 缺失会降低髁突软骨中 TMJ 软骨细胞的增殖。此外，Kindlin-2 的缺失会促进细胞色素 c 的释放以及 caspase 3 的激活，并加速体外和 TMJ 软骨细胞的凋亡。总的来说，这些发现揭示了 Kindlin-2 在髁突软骨细胞中维持 TMJ 稳态的关键作用。