title: BMP Signaling Mediated by BMPR1A in Osteoclasts Negatively Regulates Osteoblast Mineralization Through Suppression of Cx43.
abstract: 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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, 130021, China.|Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan, 48109-1078.
authors.forename: Ce
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan, 48109-1078.
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan, 48109-1078.
authors.forename: Ke'ale
authors.initials: K
authors.lastname: Louie
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan, 48109-1078.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
authors.affiliation: Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D018031:Connexin 43; C543076:GJA1 protein, mouse; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: BMPR1A; CONNEXIN 43/GJA1; GAP JUNCTION; OSTEOBLAST; OSTEOCLAST