Biological and Mechanical Factors and Epigenetic Regulation Involved in Tendon Healing

Table 1

Influencing factors in tendon healing process.

Factor		Effects on tendon healing
Mechanical factors	Overloading	Helps the middle tendon repair but inhibits healing at the enthesis.	[139, 177–179]
	Underloading	Inhibits the middle tendon repair but helps healing at the enthesis.	[177–180]
Transcription factors	Scx, EGR1, and Mohawk	Promote tendon repair and regeneration and provide conditions conducive to cell differentiation.	[2]
Signaling	TGF-β	Involved in initial inflammatory responses, collagen synthesis, and angiogenesis.	[79]
	VEGF	Promotes angiogenesis and fibroblast proliferation and activates the synthesis of other growth factors.	[79]
	FGF	Involved in inflammation, angiogenesis, cell proliferation, and collagen synthesis.	[79]
	PDGF	Promotes angiogenesis, ECM synthesis, tenoblast migration, and differentiation.	[79]
	IGF	Promotes collagen synthesis in fibroblasts and ECM synthesis.	[79]
	BMP	Improves molecular, organizational, and mechanical properties of healing tendon.	[181–184]
Epigenetic regulation	miRNA and lncRNA	Guide tendon stem cell differentiation and tissue regeneration, promote tendon healing, and reduce adhesion.	[161–163]

EGR1: early growth response 1; Scx: scleraxis; TGF-β: transformational growth factor-beta; VEGF: vascular endothelial growth factor; FGF: fibroblast growth factor; PDGF: platelet-derived growth factor; ECM: extracellular matrix; IGF: insulin-like growth factor; BMP: bone morphogenetic protein.