Gene Modification of Mesenchymal Stem Cells and Articular Chondrocytes to Enhance Chondrogenesis

Table 1

Candidate genes to enhance chondrogenesis in MSCs and dedifferentiated chondrocytes.

Overexpressed factor	Cell type	Outcome	References
TGFβ-1	Human bone marrow derived MSCs, rabbit bone marrow MSCs	Enhanced chondrogenic differentiation through Smad signalling, downregulation of sonic hedgehog signalling	[19, 20]; [48, 82]
BMP-2	Human bone marrow derived MSCs, perichondrial/periosteal cells, and adipose derived stem cells	Enhanced chondrogenesis driven by Sox9 activated collagen II and aggrecan synthesis, accelerated chondrocyte hypertrophy	[43, 44]; [19, 20]; [45]
TGFβ-3	Rat adipose derived stem cells, porcine synovium derived MSCs	Enhanced chondrogenic potential and high resistance to fibro cartilage formation	[8, 83, 84]
BMP-7	Equine chondrocytes	Early onset of cartilage specific matrix synthesis, resistance to chondrocyte hypertrophy	[18, 46]
IGF-1	Rabbit articular chondrocytes, human bone marrow derived MSCs	Chondrocyte proliferation, enhanced wound healing potential in osteochondral defects, enhanced extracellular matrix synthesis	[53–55]; [19, 20]; [56, 57, 60]
FGF-2	Rabbit articular chondrocytes	High rate of cell proliferation, enhanced collagen II expression and formation of fibrocartilage	[58–60]
SMAD-3	Human MSCs	Activation of Sox9 resulting in collagen II over expression	[33, 34]
SOX-9	Mouse MSCs, human chondrocytes (normal and osteoarthritic), human bone marrow derived MSCs	Binding to col2a1 enhancer increases collagen II synthesis	[6, 32, 35, 36, 39–41, 65]
BARX-2	Mouse embryonic MSCs	Cell aggregation, association with Sox9 to bind and enhance collagen II expression	[42]
Klf4/c-Myc	Mouse dermal fibroblast, human dermal fibroblasts	Direct differentiation of dermal fibroblast to chondrocytes with high expression of articular chondrocyte phenotype	[22, 63]
hTeRT	Human chondrocytes, human placenta derived MSCs, human bone marrow derived MSCs,	Enhanced cell proliferation while maintaining the capacity for chondrogenic differentiation	[64, 66–69]
IL-1Ra	Human synovial fibroblast	Reduction in inflammation in joint capsule	[7]