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 adhes...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 Runx2and 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.展开更多
The treatment of pathological fractures of the femoral neck and trochanteric region secondary to benignlesions can be a challenge for orthopaedic surgeons because of the size and nature of the lesions, the resulting ...The treatment of pathological fractures of the femoral neck and trochanteric region secondary to benignlesions can be a challenge for orthopaedic surgeons because of the size and nature of the lesions, the resulting bony defect, the risk of recurrence, the possible associated deformities, and the risk of osteonecrosis. Numerous treatment modalities have been reported for the management of pathological fractures of the proximal femur secondary to benign lesions. An unsatisfactory outcome in 25% of patients and a complication rate of 45% have been observed.展开更多
基金supported, in part, by the National Key Research and Development Program of China Grants (2019YFA0906004)the National Natural Science Foundation of China Grants (81991513, 81870532, 82172375)+1 种基金the Guangdong Provincial Science and Technology Innovation Council Grant (2017B030301018)the Shenzhen Municipal Science and Technology Innovation Council Grant (20200925150409001)。
文摘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 Runx2and 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.
文摘The treatment of pathological fractures of the femoral neck and trochanteric region secondary to benignlesions can be a challenge for orthopaedic surgeons because of the size and nature of the lesions, the resulting bony defect, the risk of recurrence, the possible associated deformities, and the risk of osteonecrosis. Numerous treatment modalities have been reported for the management of pathological fractures of the proximal femur secondary to benign lesions. An unsatisfactory outcome in 25% of patients and a complication rate of 45% have been observed.
