Salidroside inhibits osteoclast differentiation based on osteoblast-osteoclast interaction via HIF-1a pathway.
10.1016/S1875-5364(25)60864-8
- Author:
Yutong JIN
1
;
Yao WANG
2
;
Chuan WANG
3
;
Lingling ZHANG
2
;
Dandan GAO
2
;
Haizhao LIU
2
;
Qingwen CAO
2
;
Chenchen TIAN
2
;
Yuhong BIAN
4
,
5
;
Yue WANG
5
,
6
Author Information
1. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
2. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
3. Department of Stomatology, NHC Key Laboratory of Hormones and Development, Chu Hsien- I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China; Department of Stomatology, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin 300134, China.
4. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: bianyuhong_2012@
5. com.
6. School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: wangyue6808@
- Publication Type:Journal Article
- Keywords:
Hypoxia-inducible factor-1a;
Osteoblast;
Osteoclast;
Osteoclastogenesis;
Salidroside
- MeSH:
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
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(5):572-584
- CountryChina
- Language:English
-
Abstract:
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.
