Regulation of cytokine-dependent calcification of cartilage tissue by NPP1 and syndecan-4

骨组织的钙化发生在骨骼纵向生长的生理过程中，但也可在骨骼系统疾病如骨关节炎（OA）中引起。在生理学上，病理组织钙化与软骨细胞分化有关，核苷酸焦磷酸酶磷酸二酯酶NPP1参与了这一过程。此外，一些数据表明，炎症因子如白细胞介素(IL)-1通过抑制NPP1促进组织钙化。基于我们小组之前的工作，将OA软骨钙化与软骨细胞肥大联系起来，并证明跨膜硫酸肝素蛋白聚糖syndecan-4参与IL-1信号传导，我们想研究NPP1和syndecan-4对软骨钙化的调节。通过离体软骨细胞和成骨细胞的体外实验以及NPP1-和syndecan-4缺失小鼠的体内研究，我们希望遵循IL-1等炎症介质通过调节NPP1促进OA组织钙化的假设，并且syndecan-4参与了这一过程。该项目将为OA发病过程中软骨病理性钙化的作用和机制提供重要见解。

Calcification of tissue occurs physiologically during the longitudinal growth of bones but is induced also in diseases of the skeletal system such as osteoarthritis (OA). As in physiology, pathological tissue calcification is linked to chondrocyte differentiation, and the nucleotide pyrophosphatase phosphodiesterase NPP1 has been implicated in this process. Moreover, some data indicate that inflammatory factors such as interleukin (IL)-1 promote tissue calcification through suppression of NPP1. Based on previous work of our group that has linked cartilage calcification in OA to chondrocyte hypertrophy and demonstrated the involvement of the transmembrane heparan sulfate proteoglycan syndecan-4 in IL-1 signalling, we want to investigate the regulation of cartilage calcification by NPP1 and syndecan-4. Through in vitro experiments on isolated chondrocytes and osteoblasts as well as in vivo studies in NPP1- and syndecan-4 deficient mice, we want to follow the hypothesis that inflammatory mediators such as IL-1 promote tissue calcification in OA by regulating NPP1 and that syndecan-4 is involved in this process. The project will provide important insights into the role and mechanisms of pathological calcification of cartilage in the pathogenesis of OA.