PTEN Regulates Matrix Synthesis in Adult Human Chondrocytes under Oxidative Stress
PTEN Regulates Matrix Synthesis in Adult Human Chondrocytes under Oxidative Stress
复制标题
DOI：
10.1002/jor.22506
复制
发表时间：
2014-02-01
影响因子：
2.8
通讯作者：
Kurosaka, Masahiro
中科院分区：
文献类型：
--
作者：
Iwasa, Kenjiro;Hayashi, Shinya;Kurosaka, Masahiro
10号染色体上缺失的磷酸酶和张力蛋白同源基因（PTEN）是一个重要的抑癌基因。PTEN作为磷酸肌醇-3-激酶（PI 3 K）-Akt和MEK/ERK信号传导的负调节剂起作用。PI 3 K-Akt通路对于细胞存活、分化和基质合成至关重要。氧化应激被认为是骨关节炎（OA）发病和进展的关键因素。因此，我们研究了氧化应激下OA软骨细胞中PTEN的功能。软骨细胞用胰岛素样生长因子-1（IGF-1）和/或叔丁基过氧化氢（tBHP）处理，这会引起氧化应激。实时荧光定量PCR检测细胞内2型胶原（Col 2a 1）和聚集蛋白聚糖（aggrecan）的表达水平，Western blotting检测Akt和ERK 1/2的磷酸化水平。软骨细胞用PTEN特异性小干扰RNA（siRNA）以及IGF-1和/或tBHP处理。OA软骨细胞中PTEN和IGF-1表达增加。PTEN表达下调增加了Col 2a 1和聚集蛋白聚糖的表达水平，并增加了氧化应激下蛋白聚糖的合成。氧化应激降低Akt的磷酸化水平，增加ERK 1/2的磷酸化水平。PTEN表达下调可增加Akt磷酸化，但不增加ERK 1/2磷酸化。我们的研究结果表明，在氧化应激下，PTEN通过PI 3 K-Akt途径调节基质合成。(c)2013骨科研究学会。出版社：Wiley Periodicals，Inc. J Orthop Res 32：231-237，2014.
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was identified as an important tumor suppressor gene. PTEN functions as a negative regulator of phosphoinositol-3-kinase (PI3K)-Akt and MEK/ERK signaling. The PI3K-Akt pathway is critical for cell survival, differentiation, and matrix synthesis. Oxidative stress is considered a critical factor in the onset and progression of osteoarthritis (OA). Therefore, we investigated the function of PTEN in OA chondrocytes under oxidative stress. Chondrocytes were treated with insulin-like growth factor-1 (IGF-1) and/or tert-butyl hydroperoxide (tBHP), which causes oxidative stress. The expression levels of type2 collagen (Col2a1) and aggrecan were analyzed by real-time PCR, and phosphorylation of Akt and ERK1/2 was analyzed by Western blotting. Chondrocytes were treated with PTEN-specific small interfering RNA (siRNA), as well as IGF-1 and/or tBHP. PTEN and IGF-1 expressions in OA chondrocytes were increased. The downregulation of PTEN expression increased the expression levels of Col2a1 and aggrecan, and increased proteoglycan synthesis under oxidative stress. Oxidative stress decreased the phosphorylation of Akt and increased that of ERK1/2. The downregulation of PTEN expression increased Akt phosphorylation, but did not increase that of ERK 1/2. Our results suggest that PTEN regulates matrix synthesis via the PI3K-Akt pathway under oxidative stress. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:231-237, 2014.