Premium
Connexin43 Gap Junctions and the Control of Skeletal Remodeling
Author(s) -
Stains Joseph P
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.200.3
Subject(s) - connexin , microbiology and biotechnology , gap junction , bone remodeling , runx2 , osteoblast , regulator , signal transduction , phenotype , osteocyte , biology , neuroscience , chemistry , in vitro , endocrinology , gene , genetics , intracellular
Osteoblasts, osteoprogenitors, and osteocytes share and amplify signals through connexin43‐containing gap junctions, coordinating their function in response to local and systemic cues. Thus, connexin43 helps orchestrate bone formation and remodeling to maintain cortical bone integrity. Loss or defects in connexin43 lead to alterations in cortical bone quality and skeletal dysplasia. Using in vitro and in vivo models, our data show how connexin43 regulates the differentiation and activity of osteoblasts and development of skeletal elements through the control of signaling pathways that converge on Runx2, a transcriptional regulator of the osteoblast lineage. In addition, our data show how connexin43 can regulate signal transduction cascades by recruiting signaling complexes to the connexin43 C‐terminus, and how loss of this function can recapitulate many of the skeletal phenotypes caused by loss of connexin43 protein in bone. Work with chimeric connexins composed of connexin43 and connexin45, two connexins with opposing biological functions in bone, underscores that both the connexin channel (e.g., pore function) and connexin C‐terminal tail (e.g., signal complexing docking function) act in concert to regulate downstream signaling. Finally, our preliminary data shows that communication of the second messenger, cAMP, through connexin43 gap junctions spatially coordinates bone formation by linking cell populations across surprisingly large distances. Support or Funding Information This work was supported by a grant, R01‐AR063631 (JPS), from the National Institutes of Health/National Institute for Arthritis, Musculoskeletal and Skin Diseases. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .