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

被引:14
|
作者
Zhang, Honghao [1 ]
Zhang, Yanshuai [1 ]
Terajima, Masahiko [2 ]
Romanowicz, Genevieve [1 ]
Liu, Yangjia [1 ,3 ]
Omi, Maiko [1 ]
Bigelow, Erin [4 ]
Joiner, Danese M. [4 ]
Waldorff, Erik, I [4 ]
Zhu, Peizhi [5 ]
Raghavan, Mekhala [5 ]
Lynch, Michelle [1 ]
Kamiya, Nobuhiro [1 ,6 ]
Zhang, Rongqing [3 ]
Jepsen, Karl J. [4 ]
Goldstein, Steve [4 ]
Morris, Michael D. [5 ]
Yamauchi, Mitsuo [2 ]
Kohn, David H. [1 ]
Mishina, Yuji [1 ]
机构
[1] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 N Univ Ave, Ann Arbor, MI 48109 USA
[2] Univ N Carolina, Sch Dent, Chapel Hill, NC 27515 USA
[3] Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China
[4] Univ Michigan, Dept Orthopaed Surg, Michigan Med, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Coll Literature Sci & Arts, Dept Chem, Ann Arbor, MI 48109 USA
[6] Tenri Univ, Nara, Japan
基金
美国国家卫生研究院;
关键词
BMP receptor type 1A; Osteoblasts; Collagen cross-links; Bone quality; Biomechanical properties; COLLAGEN CROSS-LINKING; IA RECEPTOR BMPRIA; TISSUE DIFFERENTIATION; MECHANICAL-PROPERTIES; MINERAL DENSITY; FEMORAL-NECK; LONG-BONE; MASS; FRACTURE; PROTEIN;
D O I
10.1016/j.bone.2020.115402
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 tissuelevels 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.
引用
收藏
页数:12
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