ArticleMolecular medicine (Cambridge, Mass.)2022
Tetrandrine inhibits RANKL-induced osteoclastogenesis by promoting the degradation of TRAIL.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Research progress on the intervention of osteoporosis by Chinese herbal monomers based on the Nrf2/NF-κB/MAPK pathway.Frontiers in endocrinology · 2026Review
- Therapeutic potential of natural products from Traditional Chinese Medicine in the treatment of osteoporosis.Frontiers in pharmacology · 2026Review
- Article
- Exploring the Association Between Immune Cell Phenotypes and Osteoporosis Mediated by Inflammatory Cytokines: Insights from GWAS and Single-Cell Transcriptomics.ImmunoTargets and therapy · 2025Article
- Exploring the causal genetic relationship between 41 inflammatory cytokines and osteoporosis: a bidirectional Mendelian randomization analysis.SAGE open medicine · 2025Article
- Article
- Systemic Inflammatory Regulators Associated with Osteoporosis: A Bidirectional Mendelian Randomization Study.Calcified tissue international · 2024Article
- Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis.Frontiers in immunology · 2023Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTetrandrine, a bisbenzylisoquinoline (BBI) alkaloid extracted from Stephania tetrandra (S. Moore), and is widely used in several diseases such as tuberculosis, hyperglycemia, malaria, and tumors. Tetrandrine was recently shown to prevent bone loss in ovariectomized mice. However, the specific mechanism underlying osteoclastogenesis inhibition remains unclear.
methodsTetrandrine's cytotoxicity to cells was determined using the Cell Counting Kit-8 assay. Tartrate-resistant acid phosphatase staining, immunofluorescence and bone resorption assay were performed to evaluate osteoclasts' differentiation and absorption capacity. The bone-forming capacity was assessed using alkaline phosphatase and Alizarin red S staining. qPCR and Western blotting were applied to assess the related genes and protein expression. Tetrandrine's impact on TRAIL was demonstrated through a co-immunoprecipitation assay. Animal experiments were performed for the detection of the therapeutic effect of Tetrandrine on osteoporosis.
resultsTetrandrine attenuated RANKL-induced osteoclastogenesis and decreased the related gene expression. The co-immunoprecipitation assay revealed that Tetrandrine administration accelerated the ubiquitination of TNF-related apoptosis-inducing ligand (TRAIL), which was subsequently degraded. Moreover, TRAIL overexpression was found to partially reverse the Tetrandrine-induced inhibition of osteoclastogenesis. Meanwhile, Tetrandrine significantly inhibited the phosphorylation of p38, p65, JNK, IKBα and IKKα/β, while the TRAIL overexpression weakened this effect. In addition, Tetrandrine promoted osteogenesis and inhibited the TRAIL expression in osteoblasts. Tetrandrine consistently improved bone destruction by stimulating bone formation and inhibiting bone resorption in an OVX-induced mouse model.
conclusionTetrandrine inhibits RANKL-induced osteoclastogenesis by promoting TRAIL degradation and promotes osteoblast differentiation, suggesting its potential in antiosteopenia pharmacotherapy.
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