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The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review

Zhenyu Wu1,2, Wang Zhan2, Longhuo Wu3

  • 1Department of Medical Imaging, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People's Republic of China.

Drug Design, Development and Therapy
|March 4, 2025
PubMed

Insights

FOXO3a protein plays a crucial role in bone and cartilage health. Upregulating FOXO3a shows promise for treating diseases like osteoporosis and osteoarthritis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Musculoskeletal disabilities stem from bone and cartilage diseases, with limited therapeutic options.
  • FOXO3a, a key transcription factor, regulates cellular processes including proliferation, apoptosis, and metabolism.
  • Signaling pathways like PI3K/AKT and MAPK influence FOXO3a activity in bone and cartilage pathologies.

Purpose of the Study:

  • To review the biological functions of FOXO3a in bone and cartilage diseases.
  • To explore FOXO3a's role in osteoporosis, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and intervertebral disc degeneration.
  • To evaluate FOXO3a as a potential therapeutic target for these conditions.

Main Methods:

  • Literature review of FOXO3a's involvement in bone and cartilage disease pathogenesis.
  • Analysis of FOXO3a's transcriptional regulation of key genes (e.g., MnSOD, CAT, BIM, BBC3, CDK6).
  • Examination of FOXO3a's impact on cellular processes like osteogenic differentiation, osteoblast proliferation, osteoclast activity, chondrocyte apoptosis, and inflammation.

Main Results:

  • FOXO3a promotes osteogenic differentiation and osteoblast proliferation.
  • FOXO3a inhibits osteoclast activity, chondrocyte apoptosis, and inflammatory responses.
  • Modulation of FOXO3a via post-translational modifications (PTMs) affects its function.

Conclusions:

  • FOXO3a exhibits protective effects in bone and cartilage diseases.
  • Upregulation of FOXO3a expression is beneficial for treating osteoporosis, osteoarthritis, and other related conditions.
  • FOXO3a represents a promising molecular target for developing novel therapeutic strategies.
Keywords:
FOXO3aankylosing spondylitisintervertebral disc degenerationosteoarthritisosteoporosisrheumatoid arthritis

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