Disruption of phosphoinositide-specific phospholipases Cγ1 contributes to extracellular matrix synthesis of human osteoarthritis chondrocytes.
Disruption of phosphoinositide-specific phospholipases Cγ1 contributes to extracellular matrix synthesis of human osteoarthritis chondrocytes.
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磷酸肌醇特异性磷脂酶 C gamma 1 的破坏有助于人骨关节炎软骨细胞的细胞外基质合成
DOI：
10.3390/ijms150813236
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发表时间：
2014-07-28
影响因子：
5.6
通讯作者：
Xia C
中科院分区：
文献类型：
--
作者：
Zeng G;Cui X;Liu Z;Zhao H;Zheng X;Zhang B;Xia C
骨关节炎（OA）是一种退行性关节疾病，其特征在于关节软骨降解，包括细胞外基质（ECM）降解和细胞丢失。磷脂酰肌醇特异性磷脂酶γ1（PLCγ1）可以通过多种信号通路调节细胞代谢。然而，这种激酶是否在人OA软骨细胞中表达和活跃，以及其在OA病理进展中的作用尚未研究。本研究旨在探讨PLCγ1在人OA软骨中的表达，并利用培养的人OA软骨细胞进一步探讨PLCγ1是否参与ECM的合成。结果表明，PLCγ1在人OA软骨细胞中高表达。在我们的进一步研究中，我们使用培养的人OA软骨细胞，结果表明，PLCγ1的抑制剂，U 73122和siRNA的中断有助于ECM合成的人OA软骨细胞通过调节ECM相关信号分子的表达，包括MMP-13，Col II，TIMP 1，Sox-9和AGG。此外，PLCγ1/IP 3/Ca（2+）/CaMK II信号轴通过触发mTOR/P70 S6 K/S6通路调控人软骨细胞ECM的合成。综上所述，我们的结果表明PLC-γ1活性在人OA软骨细胞ECM合成中起重要作用，并可能作为治疗OA的治疗靶点。
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/Ca(2+)/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.
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影响因子：
--
作者：
Maldonado M;Nam J
通讯作者：
Nam J
影响因子：
16.8
作者：
Timsah, Zahra;Ahmed, Zamal;Ladbury, John E.
通讯作者：
Ladbury, John E.
影响因子：
2
作者：
Pearle, AD;Warren, RF;Rodeo, SA
通讯作者：
Rodeo, SA
影响因子：
3.3
作者：
Edinger, AL;Thompson, CB
通讯作者：
Thompson, CB
DOI：
10.1186/1478-811x-11-3
发表时间：
2013-01-11
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Razmara M;Heldin CH;Lennartsson J
通讯作者：
Lennartsson J