Work

Subchondral H-type blood vessel formation aggravates articular cartilage degeneration through LEP-LEPR axis

Year: 2026

Type: article

Abstract: Background: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage deterioration that has resulted in severe physical and economic costs for society. Risk factors for osteoarthritis encompass genetic predisposition, mechanical influences, obesity, inflammation, and metabolic problems. Recent reports indicate that the morphological alterations of subchondral bone evolve dynamically with the advancement of osteoarthritis. A significant alteration in subchondral bone is the development of aberrant blood vessels, particularly H-type vessels. H-type arteries are essential for preserving subchondral bone homeostasis. They support nutrients and oxygen to bone tissue and eliminate waste, thereby supporting the metabolic activities of osteoblasts and osteoclasts. However, the upstream factors governing H-type arteries are yet unknown. Methods: The whole transcriptome analysis was performed by informatics using the GSE51588 dataset, which includes subchondral bone samples from OA patients, comparing the OA lesion side with the non-lesion side, and was further verified in clinical samples. Using LEP and LEPR knockout mice, the correlation between abnormal subchondral bone metabolism and LEP, LEPR, and H-type vessel formation were uncovered. Conclusion: This study reveals that the lipid metabolism pathway was highly enriched on the OA lesion, and LEP and LEPR were markedly underexpressed in the subchondral bone on the side with severe OA lesions. The causal relationship of the LEP-LEPR-CD31 signaling pathway in aging and osteoarthritis models is revealed at the overall and molecular levels. This project will provide a new theoretical basis for the pathogenesis of early OA and new ideas and targets for the clinical treatment of OA by exploring the LEP-LEPR-CD31 signaling in osteoarthritis.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1751127