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Pharmacological Targeting of Type H Endothelial Cells in Knee Osteoarthritis: From Molecular Signaling to Cellular

Chunlu Yan1, Chuangwei Sui2, Qiao Wan3

  • 1Dunhuang Medical Academy, Gansu University of Chinese Medicine, Lanzhou 730000, China.

Cells
|July 27, 2026
PubMed

The pathogenesis of knee osteoarthritis (KOA) involves bone homeostasis imbalance induced by inflammation, metabolism, age, mechanical stress, joint injury and other factors. Recently, Type H vessels (CD31hiEMCNhi endothelial cells) have emerged as a specialized endothelial cell subset that couples angiogenesis with osteogenesis. Type H angiogenesis in the diaphysis was found to be beneficial for maintaining bone homeostasis, while the abnormal proliferation of type H vessels in subchondral bone can lead to chondrocyte hypertrophy and osteophyte formation. However, the mechanism by which the abnormal proliferation of type H vessels induces KOA has not been elucidated in detail. In this review, we summarize the latest evidence on the role of type H endothelial cell function in the pathogenesis and progression of osteoarthritis (OA). We review the role of type H angiogenesis at different sites in the development and progression of OA and focus on the potential mechanisms that regulate type H angiogenesis in OA and the potential therapeutic value and significance of targeting type H angiogenesis in promoting bone regeneration and maintaining bone homeostasis. Finally, we discuss key obstacles and future directions for studying type H vessel regulation in KOA, offering an endothelial cell-based framework for understanding bone homeostasis and improving OA.

Keywords:
cell signalingknee osteoarthritissenolyticssmall molecule modulatorstype H endothelial cellsvascular–osteogenic coupling

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