Jiaxuan Fan, Yaohui Xie, Desun Liu, Rui Cui, Wei Zhang, Mengying Shen, Linzhong Cao

Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China

Correspondence: Linzhong Cao, Clinical College of Traditional Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, 73000, People’s Republic of China, Email 17393118984@163.com

Abstract: The crosstalk between H-type endothelial cells (ECs) and macrophages is critical for maintaining angiogenesis and osteogenesis in bone homeostasis. As core components of type H vessels, ECs respond to various pro-angiogenic signals, forming specialized vascular structures characterized by high expression of platelet-endothelial cell adhesion molecule-1 (CD31) and endothelial mucin (EMCN), thereby facilitating angiogenesis-osteogenesis coupling during bone formation. Macrophages, as key immune cells in the perivascular region, are primarily classified into the classically activated pro-inflammatory M1 phenotype and the selectively activated anti-inflammatory M2 phenotype, thereby performing dual functions in regulating local tissue homeostasis and innate immunity. In recent years, the complex crosstalk between type H vessel ECs and macrophages has garnered significant interest in the context of bone-related diseases. Orderly regulation of angiogenesis and bone immunity provides a new direction for preventing bone metabolic disorders such as osteoporosis and osteoarthritis. However, their interactions in bone homeostasis remain insufficiently understood, with limited clinical data available. This review comprehensively examines the intricate interactions between type H vessel ECs and macrophages with diverse phenotypes, and Insights into the signaling pathways that regulate their crosstalk, focusing on their roles in angiogenesis and osteogenesis. Furthermore, the review discusses recent interventions targeting this crosstalk and the challenges that remain. These insights may offer new perspectives on bone homeostasis and provide a theoretical foundation for developing novel therapeutic strategies.

Keywords: H-type vascular, endothelial cells, macrophages, molecular crosstalk, angiogenic-osteogenic coupling, bone homeostasis, interventions