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SOD3 regulates FLT1 to affect bone metabolism by promoting osteogenesis and inhibiting adipogenesis through PI3K/AKT

Ke Xu1, Wenchao Fei1, Wenxue Gao2

  • 1Department of Orthopedics, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Aging and Medicine, Shanghai, China; Center of Community-Based Health Research, Fudan University, Shanghai, China.

Free Radical Biology & Medicine
|December 23, 2023
PubMed

Insights

Superoxide Dismutase 3 (SOD3) promotes bone formation and inhibits fat accumulation in bone marrow, offering new therapeutic targets for osteoporosis treatment.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Bone Metabolism

Background:

  • Osteoporosis significantly impacts elderly health and longevity, necessitating research into its mechanisms for drug development.
  • Bone marrow mesenchymal stem cells (BMSCs) have potential for altering bone mass by directing their differentiation.
  • Superoxide Dismutase 3 (SOD3), an extracellular enzyme, plays roles in various organs, but its specific function in bone metabolism remains largely unknown.

Purpose of the Study:

  • To investigate the role of Superoxide Dismutase 3 (SOD3) in bone metabolism.
  • To elucidate the mechanism by which SOD3 influences osteogenesis and adipogenesis.
  • To identify molecular pathways and interactions involved in SOD3-mediated bone regulation.

Main Methods:

  • Analysis of clinical serum samples using ELISA and single-cell sequencing.
  • In vitro experiments on BMSCs to assess osteogenesis and adipogenesis.
  • In vivo studies using SOD3 knockout mice, including bone mineral density measurements, HE staining, and IHC staining.
  • Transcriptome sequencing to identify downstream targets of SOD3.
  • Western blot (WB) analysis to confirm molecular pathway involvement.

Main Results:

  • SOD3 expression positively correlates with bone mass and is primarily found in osteoblasts and adipocytes within BMSCs.
  • SOD3 promotes osteogenesis and inhibits adipogenesis in vitro.
  • SOD3 knockout mice exhibit reduced bone mineral density, increased bone marrow fat accumulation, and weakened osteogenesis.
  • SOD3 influences FLT1 expression, and FLT1 also promotes osteogenesis and inhibits adipogenesis.
  • SOD3 regulates FLT1 via the PI3K/AKT and MAPK signaling pathways.

Conclusions:

  • SOD3 plays a critical role in maintaining bone metabolism by promoting osteogenesis and inhibiting adipogenesis.
  • SOD3 exerts its effects on bone through the regulation of FLT1 expression and activation of the PI3K/AKT and MAPK pathways.
  • Targeting SOD3 and its downstream pathways presents a promising therapeutic strategy for managing osteoporosis.
Keywords:
AdipogenesisBMSCsFLT1OsteogenesisOsteoporosisSOD3

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