ArticleBone research2021
Mechanotransduction via the coordinated actions of integrins, PI3K signaling and Connexin hemichannels.
Article in Bone research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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The trial behind it
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Who cites it
52 citing papers in PubMed.
- The mechano-immune-vesicle regulatory circuit: a systems framework for bone homeostasis and regeneration.Bioactive materials · 2026Review
- Piezo1 Activation Rescues Anabolic Response to Mechanical Loading in Aged Bone via Connexin 43 Hemichannels.Aging cell · 2026Article
- Piezo1, Integrins, and YAP/TAZ in Osteoporotic Mechanotransduction: Key Pathways, Crosstalk, and Therapeutic Implications.Calcified tissue international · 2026Review
- Tunnelling Nanotube-Mediated Lysosome Sharing Promotes Osteocyte Survival via Transcellular Autophagy.Cell proliferation · 2026Article
- Computational insights on the interplay between electrotaxis and mechanotaxis.PLoS computational biology · 2026Article
- Periodontitis as a Model for Inflammatory Uncoupling of Bone Remodeling.Journal of periodontal research · 2026Review
- Geometry-driven immunomodulation in 3D-printed bioceramics: Negative curvature promotes macrophage M2 polarization via Ras-MAPK/HIF-1α signaling for vascularized osteogenesis.Bioactive materials · 2026Article
- Loss of WT1 Drives Adaptive Plasticity in CCDC6-RET Selpercatinib-Resistant Papillary Thyroid Cancer.Current issues in molecular biology · 2026Article
- Research Progress on Dance Training as a Mechanical Stimulus for the Prevention and Treatment of Osteoporosis: A Narrative Review.International journal of molecular sciences · 2026Review
- Matrix Stiffness-Induced Mechanical Memory of Periodontal Ligament Cell Promotes Osteogenesis in Periodontal Bone Repair.International dental journal · 2026Article
- Aebp1 loss in osteoprogenitors leads to skeletal defects resembling Ehlers-Danlos Syndrome by diminishing Wnt/β-catenin signaling.JCI insight · 2026Article
- Cholinergic regulation of osteocyte mechanobiology: A paradigm for bone adaptation.Science advances · 2025Article
- Piezoelectric Biomaterials for Bone Regeneration: Roadmap from Dipole to Osteogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Mechanosignaling in Osteoporosis: When Cells Feel the Force.International journal of molecular sciences · 2025Review
- Mechanotransduction and Skeletal Muscle Atrophy: The Interplay Between Focal Adhesions and Oxidative Stress.International journal of molecular sciences · 2025Review
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Targeting Long Noncoding RNA H19 in Subchondral Bone Osteocytes and the Alleviation of Cartilage Degradation in Osteoarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Osteocyte connexin hemichannels and prostaglandin EProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advanced Piezoelectric Materials, Devices, and Systems for Orthopedic Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Mechanical loading opens connexin 43 (Cx43) hemichannels (HCs), leading to the release of bone anabolic molecules, such as prostaglandins, from mechanosensitive osteocytes, which is essential for bone formation and remodeling. However, the mechanotransduction mechanism that activates HCs remains elusive. Here, we report a unique pathway by which mechanical signals are effectively transferred between integrin molecules located in different regions of the cell, resulting in HC activation. Both integrin α5 and αV were activated upon mechanical stimulation via either fluid dropping or flow shear stress (FSS). Inhibition of integrin αV activation or ablation of integrin α5 prevented HC opening on the cell body when dendrites were mechanically stimulated, suggesting mechanical transmission from the dendritic integrin αV to α5 in the cell body during HC activation. In addition, HC function was compromised in vivo, as determined by utilizing an antibody blocking αV activation and α5-deficient osteocyte-specific knockout mice. Furthermore, inhibition of integrin αV activation, but not that of α5, attenuated activation of the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway upon mechanical loading, and the inhibition of PI3K/AKT activation blocked integrin α5 activation and HC opening. Moreover, HC opening was blocked only by an anti-integrin αV antibody at low but not high FSS levels, suggesting that dendritic αV is a more sensitive mechanosensor than α5 for activating HCs. Together, these results reveal a new molecular mechanism of mechanotransduction involving the coordinated actions of integrins and PI3K/AKT in osteocytic dendritic processes and cell bodies that leads to HC opening and the release of key bone anabolic factors.
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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.