Monday, September 12, 2011

Grow Taller without Thrombospondin-1?

Thrombospondin-1 prevents excessive ossification in cartilage repair tissue induced by osteogenic protein-1.

"thrombospondin-1 (TSP-1) osteogenic protein-1 (OP-1). In miniature pigs, articular cartilage lesions in the femoral trochlea were treated by the microfracture technique and either received no further treatment (MFX), or were treated by additional application of recombinant osteogenic protein-1 (MFX+OP-1), recombinant TSP-1 (MFX+TSP-1), or a combination of both proteins (MFX+TSP-1+OP-1). Six and 26 weeks after surgery, the repair tissue and the degree of endochondral ossification were assessed by histochemical and immunohistochemical methods detecting collagen types I, II, X, TSP-1, and CD31. Microfracture treatment merely induced the formation of inferior fibrocartilaginous repair tissue. OP-1 stimulated chondrogenesis, but also induced chondrocyte hypertrophy, characterized by synthesis of collagen type X, and excessive bone formation. Application of TSP-1 inhibited inadvertant endochondral ossification, but failed to induce chondrogenesis. In contrast, the simultaneous application of both TSP-1 and OP-1 induced and maintained a permanent, nonhypertrophic chondrocyte-like phenotype within cartilage repair tissue. OP-1 and TSP-1 complement each other in a functional manner. While OP-1 induces chondrogenesis of the ingrowing cells, TSP-1 prevents their further hypertrophic differentiation and prevents excessive endochondral ossification within the lesions."

So THBS1 doesn't inhibit chondrogenesis.

"Stimulation with TSP-1 for 24 or 48 h significantly inhibited the mRNA expression of GADD45β, a factor that was recently shown to be involved in chondrocyte hypertrophy. On the contrary, single stimulation with OP-1 for 24 h significantly induced the expression of GADD45β, an effect that could be neutralized by simultaneous application of TSP-1"

BMP-7 induces both Sox9 and Runx2.

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