ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2012
Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
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Who cites it
161 citing papers in PubMed, 263 citations in OpenAlex.
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- Primary cilia in osteoblasts and osteocytes are required for skeletal development and mechano-adaptation.PloS one · 2026Article
- Skeletal abnormalities caused by a Connexin43Bone research · 2025Article
- Molecular communication from bone to skeletal muscle: an overview.Frontiers in cell and developmental biology · 2025Review
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- BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression.Cancer letters · 2024Article
- Connexin hemichannels drive lactation-induced osteocyte acidification and perilacunar-canalicular remodeling.Cell reports · 2024Article
- Regulatory cellular and molecular networks in the bone microenvironment during aging.Life medicine · 2024Review
- A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
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 (Cx43(ΔOt) 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 Cx43(ΔOt) 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.
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