title: PTEN regulates matrix synthesis in adult human chondrocytes under oxidative stress.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University, Graduate School of Medicine, Kobe, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Iwasa
authors.forename: Shinya
authors.initials: S
authors.lastname: Hayashi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Fujishiro
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kanzaki
authors.forename: Shingo
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Shuhei
authors.initials: S
authors.lastname: Sakata
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Chinzei
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000328:Adult; D053674:Aggrecans / Q000096:biosynthesis; D019902:Chondrocytes / Q000378:metabolism; D024043:Collagen Type II / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D010003:Osteoarthritis / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D011509:Proteoglycans / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D011509:Proteoglycans; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PTEN; aggrecan; chondrocytes; oxidative stress; type2 collagen