title: Deletion of BMP receptor type IB decreased bone mass in association with compromised osteoblastic differentiation of bone marrow mesenchymal progenitors.
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.
authors.affiliation: Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China.|Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, MI 48109-1078, USA.
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, MI 48109-1078, USA.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Iura
authors.affiliation: School of Dentistry, University of North Carolina, Chapel Hill, NC 27514, USA.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Terajima
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, MI 48109-1078, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.|Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA.|Orthopaedic Institute for Children, Los Angeles, CA 90007, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Lyons
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, MI 48109-1078, USA.
authors.forename: Haichun
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, MI 48109-1078, USA.
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Dentistry, University of North Carolina, Chapel Hill, NC 27514, USA.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Yamauchi
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, MI 48109-1078, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
authors.affiliation: Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, 130021, China.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Sun
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D000818:Animals; D001835:Body Weight; D001854:Bone Marrow Cells / Q000166:cytology*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology; D002454:Cell Differentiation; D003094:Collagen / Q000737:chemistry; D005260:Female; D017353:Gene Deletion; D006706:Homeostasis; D006720:Homozygote; D008024:Ligands; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology; D010012:Osteogenesis; D010641:Phenotype; D015398:Signal Transduction; D055114:X-Ray Microtomography
chemical_list: D019485:Bone Morphogenetic Proteins; D008024:Ligands; D003094:Collagen; D030201:Activin Receptors, Type I; C498943:Acvr1 protein, mouse; C498215:Bmpr1b protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I