ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2017
Evidence that activation of ASIC1a by acidosis increases osteoclast migration and adhesion by modulating integrin/Pyk2/Src signaling pathway.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2017. 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, 24 citations in OpenAlex.
- Integrin αVβ3 as a context‑dependent regulator of bone homeostasis: Insights into osteoporosis pathogenesis and therapeutic targeting (Review).Molecular medicine reports · 2026Review
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Targeting integrin αVβ3-Ptgs2-mTOR signaling rescues bone formation in osteoporosis: from molecular mechanism toward therapy.Cellular & molecular biology letters · 2026Article
- Acid-Responsive Nanocarriers for Site-Specific Osteoclast Inhibition and Osteoporosis Therapy: A Review.International journal of nanomedicine · 2026Review
- Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.Biomolecules · 2022Review
- The ASIC3-M-CSF-M2 macrophage-positive feedback loop modulates fibroblast-to-myofibroblast differentiation in skin fibrosis pathogenesis.Cell death & disease · 2022Article
- ASIC1a stimulates the resistance of human hepatocellular carcinoma by promoting EMT via the AKT/GSK3β/Snail pathway driven by TGFβ/Smad signals.Journal of cellular and molecular medicine · 2022Article
- Why SNP rs3755955 is associated with human bone mineral density? A molecular and cellular study in bone cells.Molecular and cellular biochemistry · 2022Article
- Evidence for role of acid-sensing ion channel 1a in chronic rhinosinusitis with nasal polyps.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2021Article
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.Pain reports · 2021Review
- Integrin-associated molecules and signalling cross talking in osteoclast cytoskeleton regulation.Journal of cellular and molecular medicine · 2020Review
- Acid-Sensing Ion Channel-1a in Articular Chondrocytes and Synovial Fibroblasts: A Novel Therapeutic Target for Rheumatoid Arthritis.Frontiers in immunology · 2020Review
- Extracellular vesicles in bone: "dogrobbers" in the "eternal battle field".Cell communication and signaling : CCS · 2019Review
- Regulation of TRPV5 transcription and expression by E2/ERα signalling contributes to inhibition of osteoclastogenesis.Journal of cellular and molecular medicine · 2018Article
- Comments on Bergman et al.: Bisphosphonate use after clinical fracture and risk of new fracture.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2018Article
- Long Non-coding RNAs: A New Regulatory Code for Osteoporosis.Frontiers in endocrinology · 2018Review
- Osteoclast-Derived Extracellular Vesicles: Novel Regulators of Osteoclastogenesis and Osteoclast-Osteoblasts Communication in Bone Remodeling.Frontiers in physiology · 2018Review
- PLLA Coating of Lyophilized Human Bone Allograft for Long-term Release of Antibiotics.In vivo (Athens, Greece)Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated acid-sensing ion channel 1a (ASIC1a) is involved in acid-induced osteoclastogenesis by regulating activation of the transcription factor NFATc1. These results indicated that ASIC1a activation by extracellular acid may cause osteoclast migration and adhesion through Ca
introductionOsteoclast adhesion and migration are responsible for osteoporotic bone loss. Acidic conditions promote osteoclastogenesis. ASIC1a in osteoclasts is associated with acid-induced osteoclastogenesis through modulating transcription factor NFATc1 activation. However, the influence and the detailed mechanism of ASIC1a in regulating osteoclast adhesion and migration, in response to extracellular acid, are not well characterized.
methodsIn this study, knockdown of ASIC1a was achieved in bone marrow macrophage cells using small interfering RNA (siRNA). The adhesion and migration abilities of osteoclast precursors and osteoclasts were determined by adhesion and migration assays, in vitro. Bone resorption was performed to measure osteoclast function. Cytoskeletal changes were assessed by F-actin ring formation. αvβ3 integrin expression in osteoclasts was measured by flow cytometry. Western blotting and co-immunoprecipitation were performed to measure alterations in integrin/Pyk2/Src signaling pathway.
resultsOur results showed that blockade of ASIC1a using ASIC1a-siRNA inhibited acid-induced osteoclast precursor migration and adhesion, as well as osteoclast adhesion and bone resorption; we also demonstrated that inhibition of ASIC1a decreased the cell surface αvβ3 integrin and β3 protein expression. Moreover, blocking of ASIC1a inhibited acidosis-induced actin ring formation and reduced Pyk2 and Src phosphorylation in osteoclasts and also inhibited the acid-induced association of the αvβ3 integrin/Src/Pyk2.
conclusionTogether, these results highlight a key functional role of ASIC1a/αvβ3 integrin/Pyk2/Src signaling pathway in migration and adhesion of osteoclasts.
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