Osteoarthritis (OA) is a chronic degenerative joint disease associated with cartilage damage. H-type subchondral blood vessel formation exacerbates articular cartilage degeneration via the LEP-LEPR axis. H-type blood vessels are important for subchondral bone homeostasis because they deliver nutrients, oxygen, and remove waste. Transcriptome analysis of GSE51588 data compared subchondral bone from OA lesions and without lesions in patients. The lipid metabolic pathway was highly enriched in OA lesions, and the LEP and LEPR genes were significantly underexpressed in areas with severe lesions. A correlation between abnormal subchondral bone metabolism and H-type vessel formation was demonstrated in LEP and LEPR knockout mice. The study revealed a causal relationship of the LEP-LEPR-CD31 signaling pathway in models of aging and osteoarthritis. The results provide a theoretical basis for the pathogenesis of early OA and targets for treatment.