Table 1.

Effects of different bioactive factors on MSC chondrogenic differentiation.

Bioactive factors	Cell type	Signaling pathway	Dose	Effect	Ref.
TGF-β3	Human BMSCs	Activate TGF-β/Smad pathway	10 ng/mL	Promote MSC chondrogenic differentiation	[16, 17]
TGF-β1	Rat SDSCs	Activate RhoA/ROCK pathway and Smad pathway	10 ng/mL	Induce gene expression of SOX9, COL I, COL II, and ACAN	[18]
	Human BMSCs	Activate MAPK pathway and Wnt pathway	10 ng/mL	Induce gene expression of SOX9, COL II, and ACAN and proteoglycan synthesis	[19]
BMPs	Human ADSCs and BMSCs	NA	500 ng/mL	BMP-2, BMP-4, BMP-6, and BMP-7 are effective enhancers of MSC chondrogenic differentiation	[21]
FGF-2	Human BMSCs	NA	10 ng/mL	Increase GAG/DNA content	[22]
TSP-2	Human UCBSCs	Activate Notch pathway	NA	Promote the chondrogenic differentiation of MSCs and attenuate their hypertrophic differentiation	[23]
KGN	Human ADSCs	NA	100 nM/L	Promote chondrogenic differentiation and suppress chondrocyte hypertrophy in MSCs	[30]
	Human SDSCs	Activate BMP-7/Smad5 pathway	1 μM/L and 10 μM/L	Increase gene expression of COL II and ACAN	[32]
	Human UCMSCs	Activate JNK/RUNX1 pathway and suppress β-catenin/RUNX2 pathway	1 μM/L	Elevate accumulation of extracellular matrix and chondrogenic gene expression of SOX9, COL II, and ACAN	[33]
	Human BMSCs	NA	100 nM/L	Increase gene expression of SOX9, RUNX2, SERPINB2, and SERPINA9	[34]
Melatonin	Human BMSCs	Attenuate IL-1β-induced activation of NF-κB pathway	50 nM/L	Save IL-1β-impaired MSC chondrogenic differentiation	[41]
	Human BMSCs	NA	50 nM/L	Enhance accumulation of GAG, COL II, and COL X	[42]
CS	Goat BMSCs	NA	CS-based hydrogels	Promote MSC chondrogenic differentiation and inhibit chondrocyte hypertrophy	[45]
Ghrelin	Rat BMSCs	Enhance phosphorylation of ERK1/2 and DMNT3A	10 nM/L	Upregulate expression of COL II, SOX9, and ACAN and enhance accumulation of collagen and GAG in vitro; improve cartilage repair effect of BMSCs in vivo	[50]
Atractylenolides	Rat BMSCs	Activate SHH pathway	30 μg/mL	Increase gene expression of SOX9, COL II, and ACAN	[51]
FSTL-1	Mouse MSCs	Activate TGF-β pathway	5 μg/mL	Upregulate expression of SOX9 and COL II	[53]

TGF-β: transforming growth factor beta; BMSCs: bone marrow-derived mesenchymal stem cells; MSCs: mesenchymal stem cells; SDSCs: synovial membrane-derived mesenchymal stem cells; BMPs: bone morphogenetic proteins; ADSCs: adipose tissue-derived mesenchymal stem cells; NA: not applicable; FGF-2: fibroblast growth factor-2; GAG: glycosaminoglycan; TSP-2: thrombospondin-2; UCBSCs: umbilical cord blood-derived mesenchymal stem cells: KGN: kartogenin; UCMSCs: umbilical cord-derived mesenchymal stem cells; COL II: type II collagen; COL X: type X collagen; CS: chondroitin sulfate; FSTL-1: follistatin-like protein-1.