ArticleAnnals of translational medicine2022
Hypoxia-inducible factor 1α enhances RANKL-induced osteoclast differentiation by upregulating the MAPK pathway.
Article in Annals of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Identifying adaptive variation in spatially structured populations using low-coverage whole-genome sequencing data.Molecular biology and evolution · 2026Article
- Metabolic checkpoints in bone remodeling: from dysregulation to targeted therapies.Clinics (Sao Paulo, Brazil) · 2026Review
- HALP score-adjusted FRAXplus tool effectively predicts hip fracture risk in elderly women with type 2 diabetes mellitus.BMC endocrine disorders · 2026Article
- A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt-MAPK-Nrf2-NF-κB Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- The Hypoxostat Model: A Conceptual Framework Linking Hypoxia, Oxidative Stress and Periodontal Breakdown Under Orthodontic Load.Antioxidants (Basel, Switzerland) · 2026Article
- Hypoxia-Inducible Factor 1-α in Autoimmune Diseases-Insights from the Paradigm of Hashimoto's Thyroiditis: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Plasma metabolomic and lipidomic signatures characteristic of treatment non-response in rheumatoid arthritis.Frontiers in immunology · 2026Article
- HIF-1α at the intersection of hypoxia, ferroptosis-associated stress, and cell death crosstalk in osteomyelitis.Frontiers in cell and developmental biology · 2026Review
- Vascularized in vitro bone model as 3D quadruple culture with primary human osteoblasts, osteocytes, osteoclasts and endothelial cells.Materials today. Bio · 2025Article
- Therapeutic potential of total flavonoids of Rhizoma Drynariae: inhibiting adipogenesis and promoting osteogenesis via MAPK/HIF-1α pathway in primary osteoporosis.Journal of orthopaedic surgery and research · 2025Article
- The role of hypoxic microenvironment in rheumatoid arthritis.Frontiers in immunology · 2025Review
- A Hypoxia-Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage.International journal of molecular sciences · 2024Review
- Differential but complementary roles of HIF-1α and HIF-2α in the regulation of bone homeostasis.Communications biology · 2024Article
- Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets.Molecular medicine (Cambridge, Mass.) · 2024Review
- IL-17A deficiency inhibits lung cancer-induced osteoclastogenesis by promoting apoptosis of osteoclast precursor cells.PloS one · 2024Article
- Anti-Inflammatory Effects of Dietary Polyphenols through Inhibitory Activity against Metalloproteinases.Molecules (Basel, Switzerland) · 2023Review
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Authors and funding
11 authors.
Funding
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Abstract
Background: Hypoxia (low-oxygen tension) and excessive osteoclast activation are common conditions in many bone loss diseases, such as osteoporosis, rheumatoid arthritis (RA), and pathologic fractures. Hypoxia-inducible factor 1 alpha (HIF1α) regulates cellular responses to hypoxic conditions. However, it is not yet known how HIF1α directly affects osteoclast differentiation and activation. This study sought to. explore the effects of HIF1α on osteoclast differentiation and it's molecular mechanisms. Methods: L-mimosine, a prolyl hydroxylase (PHDs) domain inhibitor, was used to stabilize HIF1α in normoxia. In the presence of receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL), RAW264.7 cells were cultured and stimulated by treatment with L-mimosine at several doses to maintain various levels of intracellular HIF1α. The multi-nucleated cells were assessed by a tartrate-resistant acid phosphatase (TRAP) and F-actin ring staining assays. The osteoclast-specific genes, such as Cathepsin K, β3-Integrin, TRAP, c-Fos, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and matrix metallo-proteinase 9 (MMP9), were analyzed by real time-polymerase chain reaction (RT-PCR). The expression of relevant proteins was analyzed by Western blot. Results: L-mimosine increased the content of intracellular HIF1α in a dose-dependent manner, which in turn promoted RANKL-induced osteoclast formation and relevant protein expression by upregulating the mitogen-activated protein kinase (MAPK) pathways. Conclusions: Our findings suggest that HIF1α directly increases the osteoclast differentiation of RANKL-mediated RAW264.7 cells
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