Cell autonomous requirement of connexin 43 for osteocyte survival: Consequences for endocortical resorption and periosteal bone formation
Open accessAbstract
Connexin 43 (Cx43) mediates osteocyte communication with other cells and with the extracellular milieu and regulates osteoblastic cell signaling and gene expression. We now report that mice lacking Cx43 in osteoblasts/osteocytes or only in osteocytes (Cx43ΔOt mice) exhibit increased osteocyte apoptosis, endocortical resorption, and periosteal bone formation, resulting in higher marrow cavity and total tissue areas measured at the femoral mid-diaphysis. Blockade of resorption reversed the increased marrow cavity but not total tissue area, demonstrating that endocortical resorption and periosteal apposition are independently regulated. Anatomical mapping of apoptotic osteocytes, osteocytic protein expression, and resorption and formation suggests that Cx43 controls osteoclast and osteoblast activity by regulating osteoprotegerin and sclerostin levels, respectively, in osteocytes located in specific areas of the cortex. Whereas empty lacunae and living osteocytes lacking osteoprotegerin were distributed throughout cortical bone in Cx43ΔOt mice, apoptotic osteocytes were preferentially located in areas containing osteoclasts, suggesting that osteoclast recruitment requires active signaling from dying osteocytes. Furthermore, Cx43 deletion in cultured osteocytic cells resulted in increased apoptosis and decreased osteoprotegerin expression. Thus, Cx43 is essential in a cell-autonomous fashion in vivo and in vitro for osteocyte survival and for controlling the expression of osteocytic genes that affect osteoclast and osteoblast function. © 2012 American Society for Bone and Mineral Research
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Disruption in cell-to-cell communication between osteocytes may induce release of local proosteoclastogenic cytokines.
“In addition, an increase in RANKL/OPG ratio expressed by osteocytes was also observed in connexin43-deficient rats, suggesting that a disruption in cell-to-cell communication between osteocytes may induce the release of local proosteoclastogenic cytokines [33, 196, 197].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [196]
In connexin43-deficient rats, osteocytes show increased RANKL/OPG ratio.
“In addition, an increase in RANKL/OPG ratio expressed by osteocytes was also observed in connexin43-deficient rats, suggesting that a disruption in cell-to-cell communication between osteocytes may induce the release of local proosteoclastogenic cytokines [33, 196, 197].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [196]
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“This research was supported by National Institutes of Health (R01-AR053643) and by a Biomedical Research Grant and a Developing Diverse Researchers with InVestigative Expertise (DRIVE) Grant from Indiana University School of Medicine.”
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Role of connexins and pannexins during ontogeny, regeneration, and pathologies of bone
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- Authors
- Bivi, N., Condon, K. W., Allen, M. R., Farlow, N., Passeri, G., Brun, L. R., Rhee, Y., Bellido, T., & Plotkin, L. I.
- Affiliations
- Indiana University Indianapolis (US)
- University of Parma (IT)
- National University of Rosario (AR)
- Yonsei University (KR)
- Corresponding author
- Plotkin, Lilian I
- ORCID
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-10-25
- Volume
- 27
- Issue
- 2
- Pages
- 374-389
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC3271138
- OpenAlex
- W2090197092
- Cited by
- 261
- References
- 78
- Citations by year
- 2026: 13 · 2025: 6 · 2024: 18 · 2023: 18 · 2022: 16 · 2021: 18 · 2020: 30 · 2019: 29 · 2018: 14 · 2017: 20 · 2016: 13 · 2015: 14 · 2014: 19 · 2013: 20 · 2012: 13
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Conicet (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK6 BX004596)
- Indiana Clinical and Translational Sciences Institute
- National Institutes of Health (1s10rr023710-01, AG13918, RR025761)
- School of Medicine, Indiana University
- National Institute on Aging (P01AG013918)
- Fogarty International Center (R03TW006919)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076007)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR059357, K02AR002127, R01AR053643)
- National Center for Research Resources (S10‐RR023710, UL1RR025761, RR-025761)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- connexin 43, osteocyte survival, osteocyte apoptosis, periosteal bone formation, osteoprotegerin, sclerostin, osteoclast recruitment, cortical bone, intercellular communication
- MeSH terms
- Animals, Bone Resorption, Cell Survival, Femur, Glycoproteins, Models, Biological, Osteoblasts, Osteocytes, Osteogenesis, Periosteum, Apoptosis, Gene Deletion, Connexin 43, Intercellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, RANK Ligand, X-Ray Microtomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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