title: Disruption of phosphoinositide-specific phospholipases Cγ1 contributes to extracellular matrix synthesis of human osteoarthritis chondrocytes.
abstract: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation including extracellular matrix (ECM) degradation and cell loss. It is known that phosphoinositide-specific phospholipase γ1 (PLCγ1) can trigger several signaling pathways to regulate cell metabolism. However, whether this kinase is expressive and active in human OA chondrocytes and its role in the pathological progression of OA have not been investigated. The current study was designed to investigate the PLCγ1 expression in human OA cartilage, and whether PLCγ1 was involved in the ECM synthesis had been further explored using cultured human OA chondrocytes. Our results indicated that PLCγ1 was highly expressed in human OA chondrocytes. In our further study using the cultured human OA chondrocytes, the results demonstrated that the disruption of PLCγ1 by its inhibitor, U73122, and siRNA contributed to the ECM synthesis of human OA chondrocytes through regulating the expression of ECM-related signaling molecules, including MMP-13, Col II, TIMP1, Sox-9, and AGG. Furthermore, PLCγ1/IP3/Ca2+/CaMK II signaling axis regulated the ECM synthesis of human chondrocytes through triggering mTOR/P70S6K/S6 pathway. In summary, our results suggested that PLC-γ1 activities played an important role in the ECM synthesis of human OA chondrocytes, and may serve as a therapeutic target for treating OA.
authors: Department of Sports Medicine & Joint Surgery, Zhongshan Hospital, Xiamen University, Fujian 361004, China. zenggqing@163.com.
authors: Guoqing
authors: G
authors: Zeng
authors: Department of Sports Medicine & Joint Surgery, Zhongshan Hospital, Xiamen University, Fujian 361004, China. cuixu666@163.com.
authors: Xu
authors: X
authors: Cui
authors: Department of Sports Medicine & Joint Surgery, Zhongshan Hospital, Xiamen University, Fujian 361004, China. 18850311056@163.com.
authors: Zejun
authors: Z
authors: Liu
authors: Department of Sports Medicine & Joint Surgery, Zhongshan Hospital, Xiamen University, Fujian 361004, China. 15960822127@163.com.
authors: Honghai
authors: H
authors: Zhao
authors: Department of Sports Medicine & Joint Surgery, Zhongshan Hospital, Xiamen University, Fujian 361004, China. zxp_635@126.com.
authors: Xinpeng
authors: X
authors: Zheng
authors: Medical School, Xiamen University, Fujian 361102, China. cristal66@xmu.edu.cn.
authors: Bing
authors: B
authors: Zhang
authors: Department of Sports Medicine & Joint Surgery, Zhongshan Hospital, Xiamen University, Fujian 361004, China. chunxia@xmu.edu.cn.
authors: Chun
authors: C
authors: Xia
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D051966:Phospholipase C gamma / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D055758:SOX9 Transcription Factor; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D051966:Phospholipase C gamma; D053509:Matrix Metalloproteinase 13