Loss of BMP signaling mediated by BMPR1A in osteoblasts leads to differential bone phenotypes in mice depending on anatomical location of the bones

Honghao Zhang, Yanshuai Zhang, Masahiko Terajima, Genevieve Romanowicz, Yangjia Liu, Maiko Omi, Erin Bigelow, Danese M. Joiner, Erik I. Waldorff, Peizhi Zhu, Mekhala Raghavan, Michelle Lynch, Nobuhiro Kamiya, Rongqing Zhang, Karl J. Jepsen, Steve Goldstein, Michael D. Morris, Mitsuo Yamauchi, David H. Kohn, Yuji Mishina

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Bone morphogenetic protein (BMP) signaling in osteoblasts plays critical roles in skeletal development and bone homeostasis. Our previous studies showed loss of function of BMPR1A, one of the type 1 receptors for BMPs, in osteoblasts results in increased trabecular bone mass in long bones due to an imbalance between bone formation and bone resorption. Decreased bone resorption was associated with an increased mature-to-immature collagen cross-link ratio and mineral-matrix ratios in the trabecular compartments, and increased tissue-level biomechanical properties. Here, we investigated the bone mass, bone composition and biomechanical properties of ribs and spines in the same genetically altered mouse line to compare outcomes by loss of BMPR1A functions in bones from different anatomic sites and developmental origins. Bone mass was significantly increased in both cortical and trabecular compartments of ribs with minimal to modest changes in compositions. While tissue-levels of biomechanical properties were not changed between control and mutant animals, whole bone levels of biomechanical properties were significantly increased in association with increased bone mass in the mutant ribs. For spines, mutant bones showed increased bone mass in both cortical and trabecular compartments with an increase of mineral content. These results emphasize the differential role of BMP signaling in osteoblasts in bones depending on their anatomical locations, functional loading requirements and developmental origin.

Original languageEnglish
Article number115402
JournalBone
Volume137
DOIs
StatePublished - Aug 2020
Externally publishedYes

Keywords

  • BMP receptor type 1A
  • Biomechanical properties
  • Bone quality
  • Collagen cross-links
  • Osteoblasts

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