ArticleExperimental & molecular medicine2021
Hypoxia-inducible factor-2α mediates senescence-associated intrinsic mechanisms of age-related bone loss.
Article in Experimental & molecular medicine, 2021. 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, 29 citations in OpenAlex.
- Tri-modal nanocatalytic microenvironment regulations for macrophage reprogramming and osteoporotic fracture healing promotion.Materials today. Bio · 2026Article
- Hypoxia Exacerbates Periapical Periodontitis-Associated Pathological Bone Loss via the Hypoxia-Inducible Factor-2α-Calmodulin-Dependent Protein Kinase IV Axis.Cell proliferation · 2026Article
- Nanoparticles coated with osteoblast-like cell membranes as curcumin delivery vehicles for targeted postmenopausal osteoporosis therapy.Materials today. Bio · 2026Article
- Bifurcate Regulation of Hematopoietic Homeostasis and Bone Osteogenesis by VHL-HIF2α-Controlled Adipocyte Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments.Clinical and translational medicine · 2025Review
- Knockdown of C3aR alleviates age-related bone loss via activation of YAP1/β-catenin signaling.The Journal of biological chemistry · 2025Article
- Differential but complementary roles of HIF-1α and HIF-2α in the regulation of bone homeostasis.Communications biology · 2024Article
- Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.International journal of molecular sciences · 2024Review
- Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging.Aging cell · 2024Review
- Intermittent hypoxia induces hepatic senescence through promoting oxidative stress in a mouse model.Sleep & breathing = Schlaf & Atmung · 2024Article
- Hedgehog signaling regulates bone homeostasis through orchestrating osteoclast differentiation and osteoclast-osteoblast coupling.Cellular and molecular life sciences : CMLS · 2023Article
- Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss.International journal of molecular sciences · 2023Review
- Hypoxia-Inducible Factor-2α Signaling in the Skeletal System.JBMR plus · 2023Review
- Hypoxia Pathway in Osteoporosis: Laboratory Data for Clinical Prospects.International journal of environmental research and public health · 2023Review
- Targeting cellular senescence in senile osteoporosis: therapeutic potential of traditional Chinese medicine.Frontiers in medicine · 2023Review
- Cuproptosis-a potential target for the treatment of osteoporosis.Frontiers in endocrinology · 2023Review
- Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair.International journal of molecular sciences · 2022Review
- Cell energy metabolism and bone formation.Bone reports · 2022Article
- Anti-Viral Activities of Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Against Human Respiratory Viruses.Frontiers in cellular and infection microbiology · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is associated with cellular senescence followed by bone loss leading to bone fragility in humans. However, the regulators associated with cellular senescence in aged bones need to be identified. Hypoxia-inducible factor (HIF)-2α regulates bone remodeling via the differentiation of osteoblasts and osteoclasts. Here, we report that HIF-2α expression was highly upregulated in aged bones. HIF-2α depletion in male mice reversed age-induced bone loss, as evidenced by an increase in the number of osteoblasts and a decrease in the number of osteoclasts. In an in vitro model of doxorubicin-mediated senescence, the expression of Hif-2α and p21, a senescence marker gene, was enhanced, and osteoblastic differentiation of primary mouse calvarial preosteoblast cells was inhibited. Inhibition of senescence-induced upregulation of HIF-2α expression during matrix maturation, but not during the proliferation stage of osteoblast differentiation, reversed the age-related decrease in Runx2 and Ocn expression. However, HIF-2α knockdown did not affect p21 expression or senescence progression, indicating that HIF-2α expression upregulation in senescent osteoblasts may be a result of aging rather than a cause of cellular senescence. Osteoclasts are known to induce a senescent phenotype during in vitro osteoclastogenesis. Consistent with increased HIF-2α expression, the expression of p16 and p21 was upregulated during osteoclastogenesis of bone marrow macrophages. ChIP following overexpression or knockdown of HIF-2α using adenovirus revealed that p16 and p21 are direct targets of HIF-2α in osteoclasts. Osteoblast-specific (Hif-2α
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