title: Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis.
abstract: BACKGROUND Although it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown. MATERIAL AND METHODS The current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures. RESULTS While the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin. CONCLUSIONS Our results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss.
authors.affiliation: Department of Orthopaedic Traumatology, Tianjin Hospital, Tianjin, China (mainland).
authors.forename: Guixin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Traumatology, Tianjin Hospital, Tianjin, China (mainland).
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics & Microsurgery, Guangdong No. 2 Provincial People's Hospital, Guanghzou, China (mainland).
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Orthopaedic Traumatology, Tianjin Hospital, Tianjin, China (mainland).
authors.forename: Jingyi
authors.initials: J
authors.lastname: Xin
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics & Microsurgery, Guangdong No. 2 Provincial People's Hospital, Guanghzou, China (mainland).
authors.forename: Dong
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Orthopedics & Microsurgery, Guangdong No. 2 Provincial People's Hospital, Guangzhou, Guangdong, China (mainland).
authors.forename: Weichi
authors.initials: W
authors.lastname: Wu
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001854:Bone Marrow Cells / Q000473:pathology; D001862:Bone Resorption / Q000097:blood / Q000209:etiology* / Q000473:pathology*; D000071556:Cancellous Bone / Q000473:pathology; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D000860:Hypoxia / Q000150:complications*; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis; D010052:Ovariectomy; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers