骨关节炎（osteoarthritis，OA）是常见的难治性关节疾病，其发病机制尚未明确。PKC-δ是新型PKC家族的一员，其表达及激活与软骨细胞的增殖、分化、凋亡有关。MAPK/NF-κB通路是引起软骨细胞凋亡的主要信号通路。本课题组前期发现PKC-δ在OA软骨组织中高表达，并与软骨细胞凋亡率呈正相关，使用PKC-δ抑制剂可减轻软骨破坏。基于前期的研究结果，我们提出以下设想：PKC-δ通过MAPK/NF-κB信号通路调控软骨细胞凋亡从而促进OA的发生发展。本课题拟通过临床组织标本、体外细胞水平、动物模拟实验等三个层面，采用qRT-PCR、免疫组化、RNA干扰、Western blot、基因敲除小鼠OA模型及免疫共沉淀联合质谱分析等手段，探讨OA中PKC-δ激活后通过MAPK/NF-κB信号通路促进软骨细胞凋亡的分子机制，以阐明PKC-δ 在OA发生发展中的作用机制。

Osteoarthritis(OA) is considered as a refractory chronic arthritis, of which mechanism is unclear. PKC-δ is a isoform of novel PKCs. PKC-δ expression and activity were associated with some cellular functions of chondrocyte including proliferation, differentiation and apoptosis. MAPK and NF-κB signaling pathway could cause cell apoptosis. Our previous study found that overexpression of PKC-δ was related with the rate of chondrocyte apoptosis in OA. And using PKC-δ inhibitor, Rottlerin could attenuate the destruction of cartilage. Based on these foundings, our hypothesis is that PKC-δ mediated chondrocyte apoptosis via MAPK/NF-κB signaling pathway in osteoarthritis. To verify this hypothesis, we plan to perform qRT-PCR, IHC, cell transfection, RNA interference, Western blot,PKC-δ knockout mice OA models，IP and MALDI-TOF/TOF-MS. In this study, we would like to investigate the effects and the underlying mechanisms of PKC-δ in chondrocyte apoptosis and MAPK/NF-κB signaling pathway in OA. The results of the study would give us a new the rapeutics for OA-inhibiting the expression and activity of PKC-δ.