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PTEN regulates matrix synthesis in adult human chondrocytes under oxidative stress
Author(s) -
Iwasa Kenjiro,
Hayashi Shinya,
Fujishiro Takaaki,
Kanzaki Noriyuki,
Hashimoto Shingo,
Sakata Shuhei,
Chinzei Nobuaki,
Nishiyama Takayuki,
Kuroda Ryosuke,
Kurosaka Masahiro
Publication year - 2014
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22506
Subject(s) - pten , tensin , protein kinase b , pi3k/akt/mtor pathway , oxidative stress , chemistry , mapk/erk pathway , downregulation and upregulation , phosphorylation , aggrecan , cancer research , microbiology and biotechnology , phosphatase , signal transduction , biology , medicine , biochemistry , gene , pathology , osteoarthritis , articular cartilage , alternative medicine
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 ( t BHP), 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 t BHP. 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. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:231–237, 2014.