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Disruption of bone morphogenetic protein type IA receptor in osteoblasts impairs bone quality and bone strength in mice

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Abstract

In recent years, several studies have found that the disruption of type IA receptor of bone morphogenetic proteins (BMPR1A) could increase bone mass. However, whether disruption of BMPR1A could have an effect on bone quality and bone strength is currently unknown. Osteoblast-targeted conditional knockout (cKO) of BMPRIA by crossing 3.2-kb Col1-CreER™ mice with BMPR1A fx +/+ mice was conducted. Then, in vitro and in vivo studies were employed to examine the effect of BMPR1A knockout on bone quality and bone strength. It was found that the ultimate force and stiffness of the femora decreased significantly in cKO mice when compared to control mice. The content of collagen and mineralization level decreased as the structure of the collagen became disorganized. The morphology of osteocytes in cKO mice was abnormal as well. The expression level of osteocalcin, a marker for the terminal differentiation of osteoblasts, decreased in cKO mice. This data indicated that the differentiation of osteoblasts in cKO mice was impaired. Immunohistochemistry examination revealed deregulated expression of dickkopf 1(DKK1) in osteocytes in cKO mice. Adding DKK1 to the culture medium reversed these effects. In conclusion, even though disruption of BMPR1A could increase bone mass, it also impairs bone quality and bone strength.

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Funding

This work was funded by National Science Foundation of China (81271935).

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Author notes

  1. Quanwei Bao and Ang Li contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Trauma, Burn and Combined Injury, Department of War Wound Rescue Skills Training, Base of Army Health Service Training, Army Medical University, ChongQing, 400038, China

    Quanwei Bao, Ang Li, Sixu Chen, Huayu Liu, Hao Qin, Junfeng Li, Daocheng Liu, Yue Shen & Zhaowen Zong

  2. Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, TX, 75246, USA

    Jianquan Feng

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  1. Quanwei Bao
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  2. Ang Li
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  3. Sixu Chen
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Correspondence to Zhaowen Zong.

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Bao, Q., Li, A., Chen, S. et al. Disruption of bone morphogenetic protein type IA receptor in osteoblasts impairs bone quality and bone strength in mice. Cell Tissue Res 374, 263–273 (2018). https://doi.org/10.1007/s00441-018-2873-3

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  • DOI: https://doi.org/10.1007/s00441-018-2873-3

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