ReviewJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2014
Shifting paradigms on the role of connexin43 in the skeletal response to mechanical load.
Review in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Activation of connexin hemichannels enhances mechanosensitivity and anabolism in disused and aged bone.JCI insight · 2024Article
- Connexin 43 in the function and homeostasis of osteocytes: a narrative review.Annals of joint · 2024Review
- Connexin 43 and cell culture substrate differentially regulate OCY454 osteocytic differentiation and signaling to primary bone cells.American journal of physiology. Cell physiology · 2023Article
- Osteocytes Exposed to Titanium Particles Inhibit Osteoblastic Cell Differentiation via Connexin 43.International journal of molecular sciences · 2023Article
- Beta 2 Adrenergic Receptor Selective Antagonist Enhances Mechanically Stimulated Bone Anabolism in Aged Mice.JBMR plus · 2023Article
- Mechanosensitive piezo1 calcium channel activates connexin 43 hemichannels through PI3K signaling pathway in bone.Cell & bioscience · 2022Article
- Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.Aging and disease · 2022Article
- Article
- Connective tissue growth factor promotes cementogenesis and cementum repair via Cx43/β-catenin axis.Stem cell research & therapy · 2022Article
- Similarities Between Disuse and Age-Induced Bone Loss.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Review
- Accumulation of advanced oxidation protein products contributes to age-related impairment of gap junction intercellular communication in osteocytes of male mice.Bone & joint research · 2022Article
- Osteocytes and Weightlessness.Current osteoporosis reports · 2021Review
- ATP transporters in the joints.Purinergic signalling · 2021Review
- Biomimetic Aspects of Oral and Dentofacial Regeneration.Biomimetics (Basel, Switzerland) · 2020Review
- The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone.International journal of molecular sciences · 2020Review
- Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts.Pflugers Archiv : European journal of physiology · 2019Article
- Overexpression of miR-27b-3p Targeting Wnt3a Regulates the Signaling Pathway of Wnt/Oxidative medicine and cellular longevity · 2019Article
- Joint diseases: from connexins to gap junctions.Nature reviews. Rheumatology · 2017Review
- Connexin43 and Runx2 Interact to Affect Cortical Bone Geometry, Skeletal Development, and Osteoblast and Osteoclast Function.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Article
- Connexin43 and the Intercellular Signaling Network Regulating Skeletal Remodeling.Current osteoporosis reports · 2017Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Gap junctions (GJs) are membrane-spanning channels that allow for the movement of small molecules across cell membranes. Connexin43 (Cx43) is the predominant GJ protein in bone. In vitro studies suggest that gap junctional intercellular communication (GJIC) sensitizes bone cells to mechanical signals. Additionally, mechanical signals detected by osteocytes are communicated to osteoblasts via GJIC, and osteocytic Cx43 hemichannels release anabolic factors, such as PGE2 and ATP, in response to mechanical load. These findings and others have led to near consensus among researchers in the field that GJIC, hemichannels or connexins facilitate the anabolic response of bone to mechanical load and, in their absence, bone would be less sensitive to load. However, recent in vivo evidence suggests the opposite is true. Studies from our laboratory and others demonstrate that Cx43-deficient mice have an increased anabolic response to mechanical load and are protected against the catabolic effects of mechanical unloading. These developments suggest a paradigm shift in our understanding of connexins, GJIC, and mechanotransduction in bone. That is, inhibiting bone cell Cx43 expression or GJIC has a beneficial effect on bone's response to its mechanical environment, preserving bone during unloading and enhancing its formation during loading. Here, we review literature in support of this hypothesis and suggest a mechanism by which Cx43, through interaction with WNT/β-catenin signaling, moderates both arms of bone remodeling.
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