Transforming Growth Factor-β-mediated Chondrogenesis of Human Mesenchymal Progenitor Cells Involves N-cadherin and Mitogen-activated Protein Kinase and Wnt Signaling Cross-talk

Articular cartilage repair by genetically modified bone marrow aspirate in sheep

“…27,28 TGF-b1 has been used as a key inductor of chondrogenesis in many in vivo and in vitro studies, as it stimulates cell proliferation and synthesis of major components of ECM, GAG and collagen. [29][30][31] It was chosen for use in this study because it is one of the best characterized and most potent chondrogenic growth factors. The results of this study showed that all groups that underwent transplantation of BMCs have a high content of GAGs, but only the repair tissue from defects treated with TGF-b1 gene plugs had a very high content of collagen type II similar to native cartilage.…”

Focus on the p38 MAPK signaling pathway in bone development and maintenance

“…Indeed, the p38 MAPK pathway is involved in the regulation of collagen 2 and aggrecan expressions, proteoglycan synthesis and cartilage nodule formation in response to those growth factors in vitro. [7][8][9] Notably, p38 signaling has been shown to positively regulate hypertrophic chondrocyte differentiation in a micromass system of mesenchymal cells recapitulating the entire chondrogenic program. 11 In this context, treatment of micromass cultures with p38 inhibitors results in a delay of hypertrophic differentiation as evidenced by reduced expressions of hypertrophic marker genes (collagen 10, tissue nonspecific alkaline phosphatase, bone sialoprotein and matrix metalloproteinase 13) and impaired mineralization.…”

“…The p38 MAPK phosphorylation and activity are increased during the course of the chondrogenic program, and inhibition of p38 blocks chondrocyte differentiation and cartilage nodule formation, 6 suggesting that this signaling pathway has an important role in chondrogenesis. Moreover, p38 MAPK has been demonstrated to be activated in response to and to mediate the effects of several growth factors essential for chondrocyte differentiation and function, including TGF-b, growth/differentiation factor 5 (GDF5), bone morphogenetic proteins (BMP) and connective tissue growth factor [7][8][9][10] ( Figure 1). Indeed, the p38 MAPK pathway is involved in the regulation of collagen 2 and aggrecan expressions, proteoglycan synthesis and cartilage nodule formation in response to those growth factors in vitro.…”

Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice

“…20,21 Oxidative stress and tissue GSH stores can modulate activation of the redox-sensitive transcription factors AP-1 and nuclear factor B, which regulate chondrogenesis. 2,[37][38][39] In addition, degradation of GSH stores by ␥-glutamyl transpeptidase critically supports intracellular levels of cysteine, a requisite mechanism to maintain endochondral chondrocyte proliferation. 21 In this study, free cysteamine alone induced sulfated proteoglycans synthesis and collagen II expression in wildtype MSCs, elevating collagen II expression in pellet culture in wild-type MSCs to levels comparable to those in cultured ank/ank MSCs without cysteamine treatment.…”

“…Chondrogenesis is a multistep transcriptionally regulated process 46 that requires recruitment and commitment of undifferentiated mesenchymal cells into chondroprogenitors, which condense in an N-cadherin-mediated manner and differentiate into chondrocytes. 39,47,48 Sox9 promotes multiple steps in this process, subject to effects of direct interaction with ␤-catenin. 1 Sox9-mediated expression of Sox5 and Sox6 further promotes condensation and chondrocyte differentiation.…”