Regulation of osteoclastogenesis by gap junction communication

AbstractReceptor activator of NF‐κB ligand (RANKL) is crucial in osteoclastogenesis but signaling events involved in osteoclast differentiation are far from complete and other signals may play a role in osteoclastogenesis. A more direct pathway for cellular crosstalk is provided by gap junction intercellular channel, which allows adjacent cells to exchange second messengers, ions, and cellular metabolites. Here we have investigated the role of gap junction communication in osteoclastogenesis in mouse bone marrow cultures. Immunoreactive sites for the gap junction protein connexin 43 (Cx43) were detected in the marrow stromal cells and in mature osteoclasts. Carbenoxolone (CBX) functionally blocked gap junction communication as demonstrated by a scrape loading Lucifer Yellow dye transfer technique. CBX caused a dose‐dependent inhibition (significant ≥ 90 µM) of the number of tartrate‐resistant acid phosphatase (TRAP)‐positive multinucleated cells formed in 7‐ to 8‐day marrow cultures stimulated by parathyroid hormone (PTH; 10 nM) or forskolin (FSK; 1 µM). Furthermore, CBX (100 µM) significantly inhibited prostaglandin E2 (PGE2; 10 µM) and 1,25(OH)2‐vitamin D3 stimulated osteoclast d