Table 3 Summary of skeleton-derived factors acting on vasculature

OCN

• Osteoblast

• Endothelial cell

• Protect vascular endothelial cell functions

• Prevent atherosclerosis progression

• Upregulate NO and NF-кB signals

• Stimulate PI3K/Akt/eNOS pathway

^127,133,137

PDGF-BB

• Preosteoclast

• Endothelial progenitor cell

• Mesenchymal stem cell

• Enhance capillary abundance

• Stabilize tube formation

• Mediate osteoblast differentiation

• Trigger PI3K/Akt signaling cascade

^141,144,145

SLIT3

• Osteoblast

• Endothelial cell

• Promote tube formation and angiogenesis

• Help bone remodeling and fracture repair

• Activate ERK mitogen-activated protein kinase and Hippo signaling pathway

^150,151

VEGF

• Osteoblast

• Chondrocyte

• Endothelial cell

• Osteoprogenitor

• Promote angiogenesis process

• Modulate bone development and homeostasis

• Induced by hypoxia via HIF-dependent pathway

• Promote induction of β-catenin and activate Wnt signaling pathway

^{156,157,158,160}

FGF

• Osteoblast

• Chondrocyte

• Endothelial cell

• Promote angiogenesis process

• Elevate vessel permeability

• Induce EC proliferation, chemotaxis, and intercellular gap-junction communication

^{165,166,167,170}

MMP

• Osteoclast

• Osteoblast

• Chondrocyte

• Endothelial cell

• Contribute to vascular lumen formation

• Via ERK, AKT, or PI3K and SRC pathways

• Release angiogenic factors (VEGF, etc.) from matrix

^{176,177,178,179,182}

LCN-2

• Osteoblast

• Adipocyte

• Endothelial cell

• Make for proper endothelial function

• Involved in cardiovascular progression

• Potentiated via IL-1β mediated pathway

^{97,184,188,189}