ArticleBone research2025
Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2.
Article in Bone research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Obeticholic acid attenuates complete freund's adjuvant-induced arthritis in rats through FXR-mediated modulation of TGF-β/TAK1/MKK3/p38 MAPK signaling, inflammation, and oxidative stress.Inflammopharmacology · 2026Article
- Osteoporosis from the perspective of the gut-bone axis: gut microbiota, metabolites, and multi-system synergistic regulation.Journal of endocrinological investigation · 2026Review
- Puerarin alleviates inflammation and promotes osteogenic differentiation in periodontitis: insights from autophagy and Notch signaling pathway.Odontology · 2026Article
- Ceramide-PKCζ signaling axis mediates burn-enhanced ectopic calcification during Achilles tendon healing.Journal of molecular histology · 2026Article
- Recapitulating Endochondral Ossification for Bone Repair: From Development to Engineering Strategy.Advanced healthcare materials · 2026Review
- Gut-bone axis crosstalk: Microbiota-driven immune-metabolic-neural networks in bone disorders and precision interventions.Journal of orthopaedic translation · 2026Review
- Dysbiosis in the Gut-Liver Axis Is Associated With Low Bone Mass During Murine Cholestasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- FXR in bone metabolism: An emerging regulator.iScience · 2026Review
- Pearl-Like Bioinspired Coating Enables Regulation of Mg Degradation for Osteoporotic Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of gut microbiota in osteoporosis: underlying mechanisms, clinical associations, and emerging biomaterials.Frontiers in immunology · 2026Review
- Integrative Single-Cell RNA Sequencing and Machine Learning Reveals Candidate Plasma Protein-Associated Gene Signatures for Osteoporosis: A Preliminary Exploratory in Silico Study.International journal of general medicine · 2026Article
- ROS-responsive adhesive nanocomposite hydrogel promotes tendon-to-bone healing by modulating the inflammatory microenvironment and pro-differentiation.Regenerative biomaterials · 2026Article
- Estrogen promotes the angiogenesis and osteogenesis of bone marrow stromal cells via regulating ESR1/RUNX2 axis.Food & nutrition research · 2026Article
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Multi-omics reveals circadian regulation of bone homeostasis by gut microbiota metabolites: mechanisms and chronotherapeutic implications.Frontiers in immunology · 2025Review
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Authors and funding
17 authors.
Funding
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Abstract
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis. Nuclear receptors (NRs) are now understood to be crucial in bone physiology and pathology. However, the function of the Farnesoid X receptor (FXR), a member of the NR family, in regulating bone homeostasis remains incompletely understood. In this study, in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells (BMSCs) and osteoblasts due to impaired osteoblast differentiation. Mechanistically, FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination, thereby promoting osteogenic activity in BMSCs. Moreover, activated FXR could directly bind to the Thoc6 promoter, suppressing its expression. The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6. Additionally, Obeticholic acid (OCA), an orally available FXR agonist, could ameliorate bone loss in an ovariectomy (OVX)-induced osteoporotic mouse model. Taken together, our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.