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<p>Disuse osteoporosis, caused by mechanical unloading, is linked to dysregulated TGFβ and BMP signaling. This study explores their roles and evaluates BMP9 as a potential therapy. A hindlimb unloading (HLU) mouse model was used to assess bone changes and signaling alterations. In vitro, a Rotary Cell Culture System (RCCS) with 3D printing simulated microgravity. BMP9 was overexpressed in bone marrow stromal cells (BMSCs) and osteocytes treated with TGFβ1. HLU mice showed reduced bone density, microstructural integrity, and dysregulated signaling (increased p-Smad2/3, decreased p-Smad1/5/8). BMP9 overexpression restored osteogenic differentiation in vitro and improved bone properties in vivo. However, RCCS failed to replicate osteogenic inhibition, likely due to shear stress. Despite challenges, BMP9 shows promise for treating disuse osteoporosis. Future research will refine vector specificity and reduce immunogenicity for clinical application.</p>

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BMP9 attenuates microgravity-related disuse osteoporosis by modulating TGFβ and BMP signaling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月1日

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  • Haoyang Zhao,
  • Mengfan Yang,
  • Yujiao Liu,
  • Xiaolin Tu,
  • Gaohai Shao

摘要

Disuse osteoporosis, caused by mechanical unloading, is linked to dysregulated TGFβ and BMP signaling. This study explores their roles and evaluates BMP9 as a potential therapy. A hindlimb unloading (HLU) mouse model was used to assess bone changes and signaling alterations. In vitro, a Rotary Cell Culture System (RCCS) with 3D printing simulated microgravity. BMP9 was overexpressed in bone marrow stromal cells (BMSCs) and osteocytes treated with TGFβ1. HLU mice showed reduced bone density, microstructural integrity, and dysregulated signaling (increased p-Smad2/3, decreased p-Smad1/5/8). BMP9 overexpression restored osteogenic differentiation in vitro and improved bone properties in vivo. However, RCCS failed to replicate osteogenic inhibition, likely due to shear stress. Despite challenges, BMP9 shows promise for treating disuse osteoporosis. Future research will refine vector specificity and reduce immunogenicity for clinical application.