ArticleJournal of orthopaedic surgery and research2022
Roxadustat promotes osteoblast differentiation and prevents estrogen deficiency-induced bone loss by stabilizing HIF-1α and activating the Wnt/β-catenin signaling pathway.
Article in Journal of orthopaedic surgery and research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- Comparative effects of roxadustat and epoetin beta on lumbar trabecular BMD in dialysis patients.Journal of bone and mineral metabolism · 2026Article
- HIF-PH Inhibitor Promotes Stabilization of HIF-1α via Inhibition of Its Degradation and Exerts Chondroprotective Effects in a Rat Osteoarthritis Model.International journal of molecular sciences · 2026Article
- Roxadustat Inhibits Osteoclast Differentiation and Function by Disrupting Cell Cycle Exit.International journal of molecular sciences · 2026Article
- LDL receptor affects the skeletal muscle and bone microstructure of female mouse through the Wnt/β-catenin signaling pathway.Journal of molecular histology · 2026Article
- Advances in the mechanism for steroid-induced osteonecrosis of the femoral head.Bone research · 2026Review
- Article
- Molecular mechanisms and translational prospects in osteoporosis.Frontiers in endocrinology · 2026Review
- Using network pharmacology and molecular docking technology, proteomics and experiments were used to verify the effect of Yigu decoction (YGD) on the expression of key genes in osteoporotic mice.Annals of medicine · 2025Article
- HIF1A overexpression promotes osteoblast differentiation through activation of autophagy to alleviate osteoporosis.Scientific reports · 2025Article
- Fused exosomal targeted therapy in periprosthetic osteolysis through regulation of bone metabolic homeostasis.Bioactive materials · 2025Article
- Molecular crosstalk in SP7-mediated osteogenesis: Regulatory mechanisms and therapeutic potential.Osteoporosis and sarcopenia · 2025Review
- PML Regulated HIF1AN Ubiquitination and Activated PI3K/AKT Pathway to Promote Bone Marrow Mesenchymal Stem Cells Osteogenic Differentiation.International journal of stem cells · 2025Article
- Hypoxic niches established via endogenous oxygen production in scaffold under anoxia for enhanced bone regeneration.Regenerative biomaterials · 2025Article
- Exploring the mechanism of Heidihuang Pill in the treatment of osteoporosis based on network pharmacology, molecular docking, and experimental validation.Frontiers in endocrinology · 2025Article
- The Physiological Functions and Therapeutic Potential of Hypoxia-Inducible Factor-1α in Vascular Calcification.Biomolecules · 2024Review
- The Bioactive Compounds ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Construction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms.International journal of molecular sciences · 2023Review
- Bioactive elements manipulate bone regeneration.Biomaterials translational · 2023Review
- Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOsteoporosis is a very common skeletal disorder that increases the risk of fractures. However, the treatment of osteoporosis is challenging. Hypoxia-inducible factor-1α (HIF-1α) plays an important role in bone metabolism. Roxadustat is a novel HIF stabilizer, and its effects on bone metabolism remain unknown. This study aimed to investigate the effects of roxadustat on osteoblast differentiation and bone remodeling in an ovariectomized (OVX) rat model.
methodsIn vitro, primary mouse calvarial osteoblasts were treated with roxadustat. Alkaline phosphatase (ALP) activity and extracellular matrix mineralization were assessed. The mRNA and protein expression levels of osteogenic markers were detected. The effects of roxadustat on the HIF-1α and Wnt/β-catenin pathways were evaluated. Furthermore, osteoblast differentiation was assessed again after HIF-1α expression knockdown or inhibition of the Wnt/β-catenin pathway. In vivo, roxadustat was administered orally to OVX rats for 12 weeks. Then, bone histomorphometric analysis was performed. The protein expression levels of the osteogenic markers HIF-1α and β-catenin in bone tissue were detected.
resultsIn vitro, roxadustat significantly increased ALP staining intensity, enhanced matrix mineralization and upregulated the expression of osteogenic markers at the mRNA and protein levels in osteoblasts compared with the control group. Roxadustat activated the HIF-1α and Wnt/β-catenin pathways. HIF-1α knockdown or Wnt/β-catenin pathway inhibition significantly attenuated roxadustat-promoted osteoblast differentiation. In vivo, roxadustat administration improved bone microarchitecture deterioration and alleviated bone loss in OVX rats by promoting bone formation and inhibiting bone resorption. Roxadustat upregulated the protein expression levels of the osteogenic markers, HIF-1α and β-catenin in the bone tissue of OVX rats.
conclusionRoxadustat promoted osteoblast differentiation and prevented bone loss in OVX rats. The use of roxadustat may be a new promising strategy to treat osteoporosis.
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