Table 2 Summary of vasculature-derived factors targeting on bone

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

^96,97,98

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

^103,104,105

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

^{117,118,119,120,121}