Results
Title

Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway.

Authors

Wang, Jianjian; Yu, Wen; Zhang, Yuxin; Chen, Bo; Meng, Zhaoxiang

Abstract

Objective: To explore the mechanism of hyperbaric oxygen therapy in inhibiting subchondral bone angiogenesis and delaying the progression of osteoarthritis through the PHD2/HIF-1α signaling pathway. Methods: Mice were randomly divided into three groups (control group, osteoarthritis group, and hyperbaric oxygen treatment group). The effect of hyperbaric oxygen therapy on osteoarthritis was evaluated using Micro-CT, Safranin O-Fast Green staining, and detection of osteoarthritis inflammation markers (MMP-13, ADAMTS-5, Col2a1, and Aggrecan). The activation relationship between PHD2 and downstream signaling pathways was investigated through gene knockout and overexpression experiments. Finally, cell scratch assays, tube formation assays, and chondrogenic differentiation experiments were conducted to verify the mechanism of the PHD2/HIF-1α signaling pathway under hyperbaric oxygen stimulation. Results: Hyperbaric oxygen therapy delayed the progression of osteoarthritis in mice. It promoted chondrogenic differentiation of mesenchymal stem cells, inhibited angiogenesis, enhanced PHD2 expression, and suppressed the production of HIF-1α and VEGFA. Silencing/overexpression of PHD2 resulted in increased/decreased production of HIF-1α and VEGFA, respectively. Conclusion: The hyperbaric oxygen environment promotes the expression of PHD2, accelerates the degradation of HIF-1α, and inhibits the production of VEGFA, thereby reducing the generation of type H vessels in subchondral bone.

Subjects

KNEE osteoarthritis; VASCULAR endothelial growth factors; PHENOMENOLOGICAL biology; RESEARCH funding; MESENCHYMAL stem cells; CELLULAR signal transduction; BIOCHEMISTRY; TRANSCRIPTION factors; DESCRIPTIVE statistics; MICE; ANIMAL experimentation; HYPERBARIC oxygenation; PATHOLOGIC neovascularization; STAINS & staining (Microscopy); DISEASE progression; BIOMARKERS

Publication

Journal of Orthopaedic Surgery & Research, 2025, Vol 20, Issue 1, p1

ISSN

1749-799X

Publication type

Academic Journal

DOI

10.1186/s13018-025-05514-8