title: HIF-1α disturbs osteoblasts and osteoclasts coupling in bone remodeling by up-regulating OPG expression.
abstract: Hypoxia-inducible factor 1α (HIF-1α) is one of the master regulators of hypoxia reactions, playing an important role in bone modeling, remodeling, and homeostasis. And overexpression of HIF-1α in mature osteoblasts through conditional deletion of the von Hippel-Lindau (VHL) gene profoundly increases angiogenesis and osteogenesis. Studies showed that mice with osteoblasts lacking Vhl had a high level of Hif-1α and increased bone mass and density. On the contrary, Hif-1α conditional knockout mice had decreased bone mass and density. Our in vitro study showed that osteoprotegerin (OPG), an essential regulator of osteoclastic activity, can be upregulated by HIF-1α and in turn downregulate the resorption activity of osteoclasts. We showed that HIF-1α may directly bind to the upstream site of OPG and enhance its expression. Our study suggested that a novel mechanism, which works via OPG signaling, may mediate the function of HIF-1α in bone remodeling.
authors: Shanghai Key Laboratory for Bone and Joint Disease, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School of the Second Military Medical University, Shanghai, China.
authors: Jin
authors: J
authors: Shao
authors: Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School of the Second Military Medical University, Shanghai, China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School of the Second Military Medical University, Shanghai, China. yangtieyi@163.com.
authors: Tieyi
authors: T
authors: Yang
authors: Shanghai Key Laboratory for Bone and Joint Disease, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Jin
authors: J
authors: Qi
authors: Shanghai Key Laboratory for Bone and Joint Disease, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Lianfang
authors: L
authors: Zhang
authors: Shanghai Key Laboratory for Bone and Joint Disease, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. denglianfu@126.com.
authors: Lianfu
authors: L
authors: Deng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016723:Bone Remodeling / Q000502:physiology*; D002478:Cells, Cultured; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053244:Osteoprotegerin; C506031:Tnfrsf11b protein, mouse
keywords: Bone remodeling; HIF-1α; Osteoblast; Osteoclast; Osteoprotegerin