Fig. 2
From: Targeting strategies for bone diseases: signaling pathways and clinical studies
Angiogenesis, homing, and the immune microenvironment in the bone marrow. a Th17 cells promote osteoclast differentiation by secreting IL-17A to upregulate RANKL, TNF-α, and IL-6, while Treg cells suppress osteogenesis by secreting inhibitory cytokines such as TGF-β, IL-4, and IL-10 and enhance WNT-10b expression via interaction with CD8+ T cells. CTLA-4 expressed by Treg cells can degrade tryptophan and promote pOC apoptosis by binding to CD80/86 on the surface of pOCs. SLIT3, PGDF-BB, and VEGF secreted by osteoblasts, osteoclasts, pOCs, and chondrocytes can promote type H angiogenesis. Endothelial Notch/Dll4 signaling can increase Noggin secretion from type H endothelial cells (ECs), which promotes osteogenesis and chondrocyte hypertrophy maturation. RANKL and MMP9 derived from type H ECs can facilitate osteoclast chemotaxis and osteoclastogenesis. b CXCR4/7, integrin α4β1 (VLA-4), and S1PR can respond to CXCL12, VCAM-1, and S1P to mediate the homing of BMSCs and pOCs. CD47 on hematopoietic stem cells (HSCs) serves as a ‘marker of self’ that binds to CD172α (S1RPα) on phagocytes to reduce depletion from mononuclear phagocyte system during homing
