The autocrine action of salidroside on osteoclast during osteoclastogenesis via hypoxia-inducible factor-1α pathway

Background and objective: The objective of this study was to investigate the potential of salidroside (SAL) (a major active compound in Rhodiola rosea L.) in regulating osteoclast differentiation and function by modulating the HIF-1 alpha pathway and its downstream target genes. Methods: The expression of HIF-1 alpha and its downstream target genes was examined at both mRNA and protein levels in osteoclasts treated with SAL. Immunofluorescence analysis was performed to assess the nuclear translocation and transcriptional activity of HIF-1 alpha in response to SAL. MTT, flow cytometry, qPCR, TRAP staining and bone resorption assays were used to evaluate the potential effect of salidroside on osteoclasts. Results: SAL enhanced the expression of HIF-1 alpha and its downstream target genes in osteoclasts. Immunofluorescence analysis confirmed the facilitation of HIF-1 alpha nuclear translocation and transcriptional activity by SAL. In addition, SAL enhanced osteoclast viability, differentiation and bone resorption activity in an autocrine manner through HIF-1 alpha/VEGF, IL-6 and ANGPTL4 pathways. Conclusion: SAL promotes osteoclast proliferation, differentiation and bone resorption through HIF-1 alpha/VEGF, IL-6 and ANGPTL4 pathways.