Evaluation of proanthocyanidins in treating Type 2 diabetic osteoporosis via SIRT6/Nrf2/GPX4 pathways

Run-Xun Ma1,2, Bing-Hao Lin1,2, Si-Xiang Feng1,2

  • 1Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Insights

Proanthocyanidins (PAC) show therapeutic potential for Type 2 diabetic osteoporosis (T2DOP). PAC treatment improves bone structure and reduces oxidative stress by activating SIRT6/Nrf2/GPX4 pathways.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Cell Biology

Background:

  • Type 2 diabetic osteoporosis (T2DOP) involves bone degradation and oxidative stress.
  • Ferroptosis, a form of regulated cell death, is implicated in T2DOP pathogenesis.
  • Impaired iron homeostasis contributes to the pathophysiology of T2DOP.

Purpose of the Study:

  • To investigate the therapeutic effects of proanthocyanidins (PAC) on T2DOP.
  • To elucidate the role of SIRT6/Nrf2/GPX4 signaling pathways in PAC's action.
  • To assess PAC's impact on bone health and oxidative stress in a T2DOP model.

Main Methods:

  • Established a T2DOP mouse model and used MC3T3-E1 cells under high glucose conditions.
  • Administered PAC to T2DOP models and control groups.
  • Analyzed bone structure using micro-CT and histological staining.
  • Assessed protein expression via Western blot and immunofluorescence.

Main Results:

  • T2DOP models exhibited reduced bone density and GPX4 expression, indicative of ferroptosis and oxidative stress.
  • PAC treatment ameliorated trabecular bone structure and decreased bone marrow adiposity.
  • PAC administration reduced oxidative stress markers and upregulated osteogenic proteins.

Conclusions:

  • Proanthocyanidins (PAC) demonstrate significant potential in treating Type 2 diabetic osteoporosis.
  • PAC exerts its therapeutic effects by modulating the SIRT6/Nrf2/GPX4 signaling cascade.
  • PAC offers a promising therapeutic strategy for managing T2DOP by combating ferroptosis and oxidative damage.