The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Enhanced Osteoclastic Resorption and Responsiveness to Mechanical Load in Gap Junction Deficient Bone
Open accessAbstract
Emerging evidence suggests that connexin mediated gap junctional intercellular communication contributes to many aspects of bone biology including bone development, maintenance of bone homeostasis and responsiveness of bone cells to diverse extracellular signals. Deletion of connexin 43, the predominant gap junction protein in bone, is embryonic lethal making it challenging to examine the role of connexin 43 in bone in vivo. However, transgenic murine models in which only osteocytes and osteoblasts are deficient in connexin 43, and which are fully viable, have recently been developed. Unfortunately, the bone phenotype of different connexin 43 deficient models has been variable. To address this issue, we used an osteocalcin driven Cre-lox system to create osteoblast and osteocyte specific connexin 43 deficient mice. These mice displayed bone loss as a result of increased bone resorption and osteoclastogenesis. The mechanism underlying this increased osteoclastogenesis included increases in the osteocytic, but not osteoblastic, RANKL/OPG ratio. Previous in vitro studies suggest that connexin 43 deficient bone cells are less responsive to biomechanical signals. Interestingly, and in contrast to in vitro studies, we found that connexin 43 deficient mice displayed an enhanced anabolic response to mechanical load. Our results suggest that transient inhibition of connexin 43 expression and gap junctional intercellular communication may prove a potentially powerful means of enhancing the anabolic response of bone to mechanical loading.
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“Conditional knockout of Cx43 in osteoblasts and osteocytes in mice led to various degrees of osteopenia depending on the differentiation state in which the deletion was induced,20,21 suggesting that functional Cx43 in osteoblasts and osteocytes is essential for normal bone mass acquisition and maintenance.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [21]
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Metadata
- Authors
- Zhang, Y., Paul, E. M., Sathyendra, V., Davison, A., Sharkey, N., Bronson, S., Srinivasan, S., Gross, T. S., & Donahue, H. J.
- Affiliations
- Pennsylvania State University (US)
- University of Washington (US)
- Corresponding author
- Donahue, Henry J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-08-29
- Volume
- 6
- Issue
- 8
- Pages
- e23516
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3163577
- OpenAlex
- W2022309828
- Cited by
- 148
- References
- 63
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 19 · 2019: 11 · 2018: 4 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 15 · 2013: 20 · 2012: 16
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Pennsylvania
- Pennsylvania State University
- National Institutes of Health
- Penn State College of Medicine
- National Institute on Aging (R01AG013087)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R03AR057546)
- 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, gap junctional intercellular communication, osteoclastogenesis, bone resorption, osteocytes, osteoblasts, RANKL/OPG ratio, mechanical loading, bone loss
- MeSH terms
- Animals, Biomechanical Phenomena, Bone and Bones, Bone Resorption, Cell Communication, Cell Line, Humans, Male, Osteoclasts, Osteocytes, Osteogenesis, RNA, Messenger, Bone Density, Gene Deletion, Gap Junctions, Connexin 43, Mice, Osteoprotegerin, RANK Ligand, Mechanical Phenomena
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