Table 1.

Summary of the effect of growth factors on chondrocytes/cartilage, synovium, and mesenchymal stem cells in vitro and in vivo

Growth factor	Chondrocytes/cartilage	Synovium	Mesenchymal stem cell	References
TGF-β1	Stimulates synthesis of ECM Decreases catabolic activity of IL-1 and MMPs	Causes synovial proliferation and fibrosis Induces chemotaxis of inflammatory leukocytes to synovium Induction of osteophyte formation	Increases proliferation and ECM production Downregulates collagen type 1 gene expression	7, 8, 27, 47, 89, 92
BMP-2	Stimulates synthesis of ECM Partial reversal of dedifferentiated phenotype in OA Increased ECM turnover (increased aggrecan degradation)	Presumed role in maturation of osteophytes Multiple injections lead to synovial fibrosis Stimulates synovial thickening in experimental OA	Increases proliferation and ECM production Downregulates collagen type 1 gene expression	10, 27, 38, 47, 92
BMP-7	Stimulates ECM synthesis Decreases cartilage degradation through decreasing activity/expression of numerous ILs and MMPs	Decreases expression of MMPs and aggrecanase Does not appear to cause osteophyte formation or synovial fibrosis	Inhibits cell proliferation Inconsistent ability to induce chondrogenesis alone Potentiates chondrogenic differentiation with TGF-βs resulting in increased ECM synthesis and decreasing collagen type 1 compared with TGF-β alone	5, 40, 65, 81, 82
IGF-I	Stimulates ECM synthesis Decreases matrix catabolism except in aged and OA cartilage	Protective effect on synovium resulting in decreased thickening and decreased evidence of chronic inflammation	Stimulates cell proliferation Increases expression of ECM Additive effect when combined with TGF-β	29, 52, 67, 96
FGF-2	Decreases aggrecanase activity Antagonizes PG synthesis Upregulates MMPs	Induces synovial proliferation Inflammatory and induces osteophyte formation when used alone	Increases PG synthesis Increases cell proliferation	24, 41, 64, 87
FGF-18	Increases chondrocyte proliferation and stimulates ECM in vitro and in injured joints but not in normal joints	Induces synovial thickening Enlargement of chondrophytes in experimental OA		24, 25, 66
PDGF	No adverse effect in normal joints	No adverse effect in normal joints	Induces proliferation	43, 57

TGF-β1 = transforming growth factor-β1; BMP = bone morphogenetic protein; IGF-I = insulin growth factor I; FGF = fibroblast growth factor; PDGF = platelet-derived growth factor; ECM = extracellular matrix; IL = interleukin; MMP = matrix metalloproteinase; OA = osteoarthritis; PG = proteoglycan.