Fig. 2

Aberrant subchondral bone remodeling in OA. OB-derived PGE2 interacts with EP4 receptors on OCs, promoting bone resorption and inducing the secretion of PDGF-BB to enhance type H angiogenesis. Furthermore, PGE2 stimulates OCs to secrete netrin1, which interacts with the DCC receptor on CGRP⁺ sensory nerves, leading to increased innervation in subchondral bone. In the OA subchondral bone, CGRP⁺ nerves stimulate EC migration through the release of SP, NPY, and VIP, which promote type H angiogenesis. The ECs involved in angiogenesis recruit MSCs through chemotaxis, thereby facilitating bone formation. The VEGF derived from OBs stimulates angiogenesis. The NGF stimulates both vascular and neural growth. Generally, the activation of SNS leads to subchondral bone resorption while suppressing bone formation through NE. OB osteoblast, PGE2 prostaglandin E2, EP prostaglandin E, OC osteoclast, PDGF-BB platelet-derived BB growth factor, DCC deleted in colorectal cancer, CGRP calcitonin-gene-related peptide, EC endothelial cell, SP substance P, NPY neuropeptide Y, VIP vasoactive intestinal peptide, MSC mesenchymal stem cells, VEGF vascular endothelial growth factor, NGF nerve growth factor, SNS sympathetic nervous system, NE norepinephrine