Friday, February 25, 2011

Protein Kinase-D

Inhibition of protein kinase-D promotes cartilage repair at injured growth plate in rats.

"Using a rat model, this study investigated potential roles of protein kinase-D (PKD) in regulating expression of osteogenic transcription factor osterix and the growth plate bony repair. 4 days post injury at the proximal tibial growth plate, rats received four once-daily injections of vehicle or 2.35mg/kg gö6976 (a PKD inhibitor), and growth plate tissues collected at day 10 were examined histologically and molecularly. In addition, effects of PKD inhibition on osteogenic and chondrogenic differentiation were examined in vitro using rat bone marrow mesenchymal stromal cells.
Compared to vehicle control, PKD inhibition caused a decrease in bone volume, an increase in % of mesenchymal tissue, and an increase in cartilaginous tissue[over twice as much] within the injury site{so maybe PKD inhibition can help form new growth plates?}. Consistently, gö6976 treatment tended to decrease expression of bone-related genes (osterix, osteocalcin) and increase levels of cartilage-related genes (Sox9, collagen-2a, collagen-10a1). In support, in vitro experiments showed that gö6976 presence in the primary rat marrow stromal cell culture resulted in a decrease of alkaline phosphatase(+) CFU-f colonies formed and an increase in collagen-2a expression in chondrogenic pellet culture.
 PKD is important for growth plate bony repair and its inhibition after growth plate injury may result in less bone formation and potentially more cartilage repair."

Full-size image (65 K)
Growth plate height looks higher in go6976 treated group and the bone seems wider.

Full-size image (136 K)"mesenchymal tissue (Me), bony trabeculae (BT), cartilaginous tissue (Ca) and bone marrow (BM)"

Notice that there is no cartilage in the selected region in the vehicle.

Sox9 was upregulated 2 fold by Go6979 treatment which was less than LSJL where one isoform of Sox9 was upregulated 3 fold.

According to The potential use of protein kinase D inhibitors for prevention/treatment of epidermal tumors., Resveratol is Protein Kinase D inhibitor.

Resveratrol is available for sale: NutriGold Resveratrol GOLD, 500mg, 120 Vegetarian Capsules - trans-Resveratrol with Grape Seed and Red Wine Polyphenols (Featuring Patented ResVinol and ORAC-15M)

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