Sunday, September 19, 2010

Src Kinase

Src kinase inhibition promotes the chondrocyte phenotype.

"The Src family kinases [regulates] the chondrocyte phenotype. The Src family kinase Lyn exhibits a dynamic expression pattern in the chondrogenic cell line ATDC5 and in a mixed population of embryonic mouse chondrocytes in high-density monolayer culture. Inhibition of Src kinase activity using the pharmacological compound PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d]pyrimidine) strongly reduced the number of primary mouse chondrocytes. In parallel, PP2 treatment increased the expression of both early markers (such as Sox9, collagen type II, aggrecan and xylosyltransferases) and late markers (collagen type X, Indian hedgehog and p57) markers of chondrocyte differentiation. PP2 repressed the expression of the Src family members Lyn, Frk and Hck. It also reversed morphological de-differentiation of chondrocytes in monolayer culture and induced rounding of chondrocytes, and reduced stress fibre formation and focal adhesion kinase phosphorylation. The Src kinase inhibitor PP2 promotes chondrogenic gene expression and morphology in monolayer culture."

PP2 reduces proliferation but increases chondrogenic gene expression.

"Lyn expression increased strongly throughout ATDC5 differentiation"

"Transcripts for the xylosyltransferases were significantly increased at days 1 and 2 (Xylt1) or days 2 and 3(Xylt2) in response to Src family inhibition"

"chondroitin sulphotransferase genes (Chst3 and Chst11) were significantly upregulated in primary chondrocyte cultures by PP2 treatment for 1 and 2 days"

"PP2 increased the expression of transcripts for the cell cycle inhibitor p57 (Cdkn1c) and for Atf3{upregulated 4 fold by LSJL}"

"Hck transcript levels were reduced by cytochalasin D and enhanced by jasplakinolide and Y27632[ROCK inhibitor]"

No comments:

Post a Comment