ArticleBone2020
TRPV4 calcium influx controls sclerostin protein loss independent of purinergic calcium oscillations.
Article in Bone, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanotransduction and musculoskeletal regeneration: Molecular mechanisms and interdisciplinary applications.Genes & diseases · 2026Review
- Exercise-responsive crosstalk within local muscle-bone units in osteosarcopenia: from mechanotransduction to secretome signalling.Frontiers in physiology · 2026Review
- Osmotic stress inhibits osteoblast differentiation and mineralization by suppressing TRPV4-mediated calcium influx.Journal of bone and mineral metabolism · 2025Article
- Mechanosignaling in Osteoporosis: When Cells Feel the Force.International journal of molecular sciences · 2025Review
- Nitric oxide contributes to rapid sclerostin protein loss following mechanical load.Biochemical and biophysical research communications · 2024Article
- Mechanotransduction in subchondral bone microenvironment and targeted interventions for osteoarthritis.Mechanobiology in medicine · 2024Review
- The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair.International journal of molecular sciences · 2024Review
- Osteocyte-mediated mechanical response controls osteoblast differentiation and function.Frontiers in physiology · 2024Review
- TRPV4 differentially controls inflammatory cytokine networks during static and dynamic compression of the intervertebral disc.JOR spine · 2023Article
- Osteoblast-lineage calcium/calmodulin-dependent kinase 2 delta and gamma regulates bone mass and quality.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis.International journal of molecular sciences · 2023Review
- The regulation and functions of the matricellular CCN proteins induced by shear stress.Journal of cell communication and signaling · 2023Review
- Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
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- Sclerostin: From Molecule to Clinical Biomarker.International journal of molecular sciences · 2022Review
- The role of TRPV channels in osteoporosis.Molecular biology reports · 2022Review
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Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Skeletal remodeling is driven in part by the osteocyte's ability to respond to its mechanical environment by regulating the abundance of sclerostin, a negative regulator of bone mass. We have recently shown that the osteocyte responds to fluid shear stress via the microtubule network-dependent activation of NADPH oxidase 2 (NOX2)-generated reactive oxygen species and subsequent opening of TRPV4 cation channels, leading to calcium influx, activation of CaMKII, and rapid sclerostin protein downregulation. In addition to the initial calcium influx, purinergic receptor signaling and calcium oscillations occur in response to mechanical load and prior to rapid sclerostin protein loss. However, the independent contributions of TRPV4-mediated calcium influx and purinergic calcium oscillations to the rapid sclerostin protein downregulation remain unclear. Here, we showed that NOX2 and TRPV4-dependent calcium influx is required for calcium oscillations, and that TRPV4 activation is both necessary and sufficient for sclerostin degradation. In contrast, calcium oscillations are neither necessary nor sufficient to acutely decrease sclerostin protein abundance. However, blocking oscillations with apyrase prevented fluid shear stress induced changes in osterix (Sp7), osteoprotegerin (Tnfrsf11b), and sclerostin (Sost) gene expression. In total, these data provide key mechanistic insights into the way bone cells translate mechanical cues to target a key effector of bone formation, sclerostin.
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What OpenQuestion holds
Registered trials
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.