This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective To study the influence of isoniazid on lymphocyte factor expression and macrophage function of rats.Methods Healthy male SD rats were randomly divided into three groups,which was treated for one month,three months and withdrawal for one month after treated for three months,and each group was randomly divided into isoniazid group and control group.The isoniazid groups were ig with isoniazid at dose of 120 mg/kg every other day and control groups were fed on normal saline.At the corresponding time points,the level of interleukin-12 (IL-12) and interferon-γ (IFN-γ) was detected with ELISA method,detected serum lysozyme content by agar plate method,and Comori method was used for the detection of acid phosphatase levels in peritoneal fluid.Results At all the time points,levels of IL-12,IFN-γ and lysozyme in isoniazid group were not significantly different compared with control group.There were statistically significant differences in acid phosphatase between isoniazid group and control group after treated for one month (P ＜ 0.05),but the significant differences disappeared at the next two time points.Conclusion Isoniazid of 120 mg/kg may have no obvious influence on the immune function of rat.We don't detect the immune injury.