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Phactr1 negatively regulates bone mass by inhibiting osteogenesis and promoting adipogenesis of BMSCs via RhoA/ROCK2

Wei Lin1,2, Zhipeng Chen3, Xiaoyi Mo1,2

  • 1Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Journal of Molecular Histology
|October 28, 2021
PubMed

Insights

Phosphatase and actin regulator 1 (Phactr1) negatively impacts bone mass by promoting fat cell formation and inhibiting bone cell development in bone marrow-derived mesenchymal stem cells (BMSCs). This occurs through the activation of RhoA/ROCK2 signaling pathways.

Area of Science:

  • Biomedical Science
  • Cell Biology
  • Stem Cell Research

Background:

  • Osteoporosis (OP) development is linked to an imbalance in osteogenic and adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs).
  • Phosphatase and actin regulator 1 (Phactr1) has been implicated in regulating BMSC differentiation, but its precise role and mechanism in OP remain unclear.

Purpose of the Study:

  • To investigate the function and underlying mechanism of Phactr1 in regulating osteogenic and adipogenic differentiation of BMSCs.
  • To determine the relationship between Phactr1 and the RhoA/ROCK2 signaling pathway in the context of BMSC differentiation and OP.

Main Methods:

  • Immunohistochemistry was used to assess Phactr1 expression in bone and adipose tissues of OP rats.
  • BMSCs were induced to undergo osteogenic and adipogenic differentiation and transfected with Phactr1 overexpression lentivirus or small interfering RNA (siRNA).
  • Western blotting, Co-immunoprecipitation (Co-IP), alizarin red staining, and Oil red O staining were employed to analyze protein expression, protein interactions, and differentiation markers.

Main Results:

  • Phactr1 expression was elevated in both bone and adipose tissues of OP rats.
  • During osteogenic differentiation, Phactr1 decreased while RhoA/ROCK2 activity increased; Phactr1 overexpression inhibited osteogenic marker Runx2.
  • During adipogenic differentiation, Phactr1 increased while RhoA activity decreased; Phactr1 knockdown inhibited adipogenic marker C/EBPα. Phactr1 interacted with ROCK2 during osteogenesis but not adipogenesis.

Conclusions:

  • Phactr1 negatively regulates bone mass by inhibiting osteogenic differentiation and promoting adipogenic differentiation of BMSCs.
  • The mechanism involves the activation of the RhoA/ROCK2 signaling pathway by Phactr1.
  • Targeting Phactr1 or the RhoA/ROCK2 pathway may offer therapeutic strategies for osteoporosis.
Keywords:
BMSCsOsteoporosisPhactr1RhoA/ROCK2

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