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.
Highlights
With the findings of Zhao Q et al, who demonstrated that bone density, bone vessels, and bone formation activity were lower in HIF-1αconditional knockout (KO) ovariectomized (OVX) mice than in wild-type OVX mice[9]
Our in vivo results showed that SAL ameliorated OVX-induced osteoporosis
The process of bone formation is reported to include initial osteoblast viability followed by increased alkaline phosphatase (ALP) activity, the development and maturation of the extracellular matrix and, mineralization[20]
Summary
With the findings of Zhao Q et al, who demonstrated that bone density, bone vessels, and bone formation activity were lower in HIF-1αconditional knockout (KO) ovariectomized (OVX) mice than in wild-type OVX mice[9]. Vhl KO OVX mice, which show increased angiogenesis and osteogenesis due to activation of the HIF-1αpathway, were protected from OVX-induced bone loss[10]. The HIF-1αpathway is a critical mediator of neoangiogenesis, which is required for skeletal regeneration. This finding suggests the application of HIF activators as therapeutics to improve bone healing. Salidroside (SAL) is a major biologically active compound extracted from the root of Rhodiolarosea L. This compound has long been used in traditional Chinese medicine. Recent studies have indicated that SAL protects cardiomyocytes against hypoxia-induced death via HIF-1αand VEGF-mediated pathway[14]. The mechanism by which SAL alters HIF-1αpathway activity was investigated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
