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Cell autonomous requirement of connexin 43 for osteocyte survival: Consequences for endocortical resorption and periosteal bone formation
Author(s) -
Bivi Nicoletta,
Condon Keith W,
Allen Matthew R,
Farlow Nathan,
Passeri Giovanni,
Brun Lucas R,
Rhee Yumie,
Bellido Teresita,
Plotkin Lilian I
Publication year - 2012
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.548
Subject(s) - osteocyte , sclerostin , osteoclast , bone resorption , osteoprotegerin , chemistry , osteoblast , microbiology and biotechnology , resorption , medicine , endocrinology , rankl , signal transduction , biology , in vitro , receptor , wnt signaling pathway , biochemistry , activator (genetics)
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. © 2012 American Society for Bone and Mineral Research