title: Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis.
abstract: Hypoxia-inducible factor (HIF)-1α plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1α expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1α-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1α signalling.
authors: Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, People's Republic of China.|Department of Pharmacology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Ling
authors: L
authors: Li
authors: Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Ye
authors: Y
authors: Qu
authors: Department of Pharmacology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Xin
authors: X
authors: Jin
authors: Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Xiao Qin
authors: XQ
authors: Guo
authors: Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, People's Republic of China.|Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Yue
authors: Y
authors: Wang
authors: Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Lin
authors: L
authors: Qi
authors: Department of Pathogenic Biology and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Jing
authors: J
authors: Yang
authors: Department of Orthopaedics, Affiliated Hospital of Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Peng
authors: P
authors: Zhang
authors: Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, People's Republic of China.|Department of Pharmaceutical Chemistry, Logistics College of Chinese People's Armed Police Forces, Tianjin, People's Republic of China.
authors: Ling Zhi
authors: LZ
authors: Li
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D003035:Cobalt / Q000633:toxicity; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010052:Ovariectomy; D010636:Phenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D005960:Glucosides; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010636:Phenols; D020011:Protective Agents; D003035:Cobalt; D000469:Alkaline Phosphatase; C018021:cobaltous chloride; C009172:rhodioloside