BMP Signaling Mediated by BMPR1A in Osteoclasts Negatively Regulates Osteoblast Mineralization Through Suppression of Cx43

Osteoblasts and osteoclasts are well orchestrated through different mechanisms of communication during bone remodeling. Previously, we found that osteoclast-specific disruption of one of the BMP receptors, Bmpr1a, results in increased osteoblastic bone formation in mice. We hypothesized that BMPR1A signaling in osteoclasts regulates production of either membrane bound proteins or secreted molecules that regulated osteoblast differentiation. In our current study, we co-cultured wild-type osteoblasts with either control osteoclasts or osteoclasts lacking BMPR1A signaling activity. We found that loss of Bmpr1a in osteoclasts promoted osteoblast mineralization in vitro. Further, we found that the expression of Cx43/Gja1 in the mutant osteoclasts was increased, which encoded for one of the gap junction proteins connexin 43/gap junction alpha 1. Knockdown of Gja1 in the mutant osteoclasts for Bmpr1a reduced osteoblastic mineralization when co-cultured. Our findings suggest that GJA1 may be one of the downstream targets of BMPR1A signaling in osteoclasts that mediates osteoclast-osteoblast communication during bone remodeling. J. Cell. Biochem. 118: 605-614, 2017. (c) 2016 Wiley Periodicals, Inc.