Table 2.
Summary of vasculature-derived factors targeting on bone
| Factors | Sources | Targets | Effects | Mechanisms | References |
|---|---|---|---|---|---|
| BMP | • Endothelial cell |
• Mesenchymal stem cell • Chondrocyte |
• Promote bone mineralized matrix formation • Promote osteogenic differentiation |
• Regulate Smad signaling pathway • Upregulate osteogenic gene expression |
64,66 |
| DII-Notch-Noggin | • Endothelial cell |
• Osteoprogenitor • Chondrocyte |
• Promote bone formation • Accelerate the hypertrophy and maturation of chondrocytes |
• Restore local expression of protein Sox9 | 73,74,76 |
| RANKL-RANK-OPG |
• Endothelial cell; • Osteoblast |
• Osteoclast • Endothelial cell |
• Regulate osteoclastogenesis process • Maintain endothelial cell integrity and survival |
• Regulate NF-κB signaling • Activate PI3K/Akt signal transduction pathway |
79,82 |
| Sema | • Endothelial cell |
• Osteoblast • Osteoclast |
• Enhance osteogenic activity • Suppress bone resorption |
• Activate Wnt/β-catenin & Rho A signaling pathway | 89,91 |
| NO | • Endothelial cell |
• Osteoblast • Osteoclast |
• Modulate osteoblast activity • Keep osteoclast-mediated bone resorption under moderation |
• Activate transcription factor NF-κB • Upregulate target genes of NOS2 and IL-1β |
96–98 |
| PG | • Endothelial cell |
• Osteoblast • Mesenchymal stem cell |
• Promote differentiation of osteoblast • Mediate BMSC adipogenic differentiation |
• Bind with EP4 signal pathway on sensory nerves • Activate Epac-dependent cyclic AMP (cAMP) signaling |
103–105 |
| Adenosine | • Endothelial cell |
• Osteoblast • Osteoclast |
• Promote osteoclast differentiation and fusion course • Enhance extracellular matrix formation and osteogenesis process |
• Drive oxidative phosphorylation in mitochondria • Activate the PLC-IP3 pathway |
111,113,114 |
| PTN | • Endothelial cell | • Osteoblast |
• Promote osteoblast recruitment and attachment to the extracellular bone matrix • Facilitate fracture healing process |
• Integrate with carboxy-terminal domain | 117–121 |
BMP Bone morphogenetic protein, Smad small mothers against decapentaplegic, Dll4 Delta-like 4, NF-κB nuclear factor-kappa B, PI3K/AKT phosphoinositide 3-kinase/protein kinase B, Sema semaphorin, NO nitric oxide, NOS nitric oxide synthase, IL-1β interleukin 1β, PG prostaglandin, EP4 prostaglandin E receptor 4, PLC phospholipase C, IP3 inositol trisphosphate, PTN pleiotrophin