Table 2.

Growth factors and their main sources, functions involved in construction of entheses

Factor		Effects	Main sources in natural forming process	Ref.
Stimulatory factors	TGF	Promote the proliferation and differentiation of mesenchymal derived cells, especially the proliferation of osteoblasts and fibroblasts Promote the expression of ECM Inhibit the growth of osteoclasts Participates in regulation of the homeostasis and remodel of the enthesis	Platelets; bone extracellular matrix	[40, 56]
	BMPs	Members of TGF family (except for BMP-1), promote the proliferation of osteoblasts and fibroblasts, as well as the formation of ECM	Osteoprogenitor cells; chondrocytes; osteoblasts; osteoclasts	[40, 56]
	FGF	Stimulate the proliferation of fibroblasts and help form the matrix	Chondrocytes; macrophages; osteoblasts	[40, 56]
	PDGF	Promote the proliferation of fibroblasts, glial cells and smooth muscle cells	Platelets; macrophages; osteoblasts	[40, 56]
	VEGF	Stimulate the growth of vascular endothelial cells, help form blood vessels in entheses and thus help maintain blood supply at the enthesis	Chondrocytes; osteoblasts; mesenchymal cell; endotheliocyte	[57]
	IGF	Promote the growth of various cells of enthuses	Chondrocytes; osteoblasts; MSCs	[57]
	GDF	Promote the growth and differentiation of various cells of entheses	MSCs; chondrocytes;	[57]
	G-CSF	Stimulate the formation of the enthesis; intensively studied	Immune cells; osteoblasts	[40, 56]
	α-SMA	Promote tunnel integration in formation of entheses	Myofibroblasts	[40]
Inhibitory factors	MMP	Breakdown the connective material between cells and adjacent tissues through degrading the extracellular matrix	Fibroblasts; leukocytes	[51]
	TNF-α	Stimulate osteoclast activity and inhibit osteoblast differentiation	Macrophages; immue cells	[51]