title: Inhibitors of Growth 1b Suppresses Peroxisome Proliferator-Activated Receptor-β/δ Expression Through Downregulation of Hypoxia-Inducible Factor 1α in Osteoblast Differentiation.
abstract: Bone formation, a highly regulated developmental process, involves osteoblast differentiation, which is controlled by different important transcription factors. Recent evidence has suggested possible negative regulation of inhibitors of growth (ING) 1b on the osteoblast marker expression. The aim of this study is to examine the detailed mechanism by which the activity of ING1b inhibits osteoblast differentiation. In the current study, we investigated the function and mechanism by which ING1b inhibits osteoblast differentiation using C3H10T1/2 mesenchymal stem cells and MC3T3-E1 preosteoblasts. Real-time polymerase chain reaction and Western blotting showed that ING1b was decreased during osteoblast differentiation and ING1b overexpression markedly decreased alkaline phosphatase (ALP) activity, runt-related transcription factor 2 (Runx2) expression, and collagen type 1 synthesis, whereas ING1b silencing significantly upregulated ALP activity, Runx2 expression, and collagen type 1 synthesis. Further studies indicated that ING1b suppressed the expression of peroxisome proliferator-activated receptor (PPAR)-β/δ in a hypoxia-inducible factor (HIF) 1α-dependent manner, while ING1b silencing significantly increased the expression of PPAR-β/δ and HIF1α. Moreover, PPAR-β/δ or HIF1α silencing significantly inhibited ALP activity, Runx2 expression, and collagen type 1 synthesis. These results demonstrated that ING1b is an important regulator of osteoblast differentiation and suppresses PPAR-β/δ. Our study may provide additional insight into osteoblast differentiation and offer a potential new molecular target for osteoporosis.
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Bo
authors: B
authors: Qu
authors: 2 Department of Neurology, West China Hospital of Sichuan University , Chengdu, Sichuan Province, China .
authors: Zhen
authors: Z
authors: Hong
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Kai
authors: K
authors: Gong
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Jun
authors: J
authors: Sheng
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Hong-Hua
authors: HH
authors: Wu
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Shao-Lin
authors: SL
authors: Deng
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Gang
authors: G
authors: Huang
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Ze-Hui
authors: ZH
authors: Ma
authors: 1 Department of Orthopedics, Chengdu Military General Hospital , Chengdu, Sichuan Province, China .
authors: Xian-Ming
authors: XM
authors: Pan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit; D015536:Down-Regulation; D015870:Gene Expression; D020868:Gene Silencing; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047494:PPAR delta; D048068:PPAR-beta; C493716:Runx2 protein, mouse; D000469:Alkaline Phosphatase