Abstract
We previously found that disruption of two type I BMP receptors, Bmpr1a and Acvr1, respectively, in an osteoblast-specific manner, increased bone mass in mice. BMPR1B, another BMP type I receptor, is also capable of binding to BMP ligands and transduce BMP signaling. However, little is known about the function of BMPR1B in bone. In this study, we investigated the bone phenotype in Bmpr1b null mice and the impacts of loss of Bmpr1b on osteoblasts and osteoclasts. We found that deletion of Bmpr1b resulted in osteopenia in 8-week-old male mice, and the phenotype was transient and gender specific. The decreased bone mass was neither due to the changes in osteoblastic bone formation activity nor osteoclastic bone resorption activity in vivo. In vitro differentiation of Bmpr1b null osteoclasts was increased but resorption activity was decreased. Calvarial pre-osteoblasts from Bmpr1b mutant showed comparable differentiation capability in vitro, while they showed increased BMP-SMAD signaling in culture. Different from calvarial pre-osteoblasts, Bmpr1b mutant bone marrow mesenchymal progenitors showed compromised differentiation in vitro, which may be a reason for the osteopenic phenotype in the mutant mice. In conclusion, our results suggested that BMPR1B plays distinct roles from BMPR1A and ACVR1 in maintaining bone mass and transducing BMP signaling.
Highlights
Bone morphogenetic proteins (BMPs) were originally identified as factors that can induce the formation of bone and cartilage when implanted at ectopic sites[1]
These results suggested that the bone phenotypes observed in Bmpr1b mutant mice are gender specific and transient
Our present results demonstrated that deletion of Bmpr1b leads to osteopenia in 8-week-old male mice
Summary
Bone morphogenetic proteins (BMPs) were originally identified as factors that can induce the formation of bone and cartilage when implanted at ectopic sites[1]. We reported that an osteoblast-specific deletion of Bmpr1a or Acvr[1] results in increased bone mass[6,7,8,9,10]. We investigated the bone phenotype of Bmpr1b null mice in vivo and the effects of Bmpr1b deletion on osteoclasts and osteoblastic lineage cells in vitro. We compared BMP-SMAD and non-SMAD signaling mediated by different BMP type I receptors and found that deletion of Bmpr1b sensitized BMP-SMAD signaling in cultured calvarial pre-osteoblasts, which was different from the other two BMP type I receptors. We identified that BMPR1B plays distinct roles in maintaining bone homeostasis and transducing BMP signaling compared with ACVR1 and BMPR1A
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