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Brief exposure to high-dose transforming growth factor-beta1 enhances periosteal chondrogenesis in vitro: a
Yasushi Miura1, Javad Parvizi, James S Fitzsimmons
1The Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA.
Background:
Articular cartilage has limited potential for repair. There have been various attempts aimed at improving the repair process in articular cartilage. Transforming growth factor-beta1 (TGF-beta1) has a stimulatory effect on chondrogenesis in periosteal explants. The purpose of the present study was to determine the effect of brief exposures (i.e., thirty and sixty minutes) of high concentrations of TGF-beta1 on periosteal chondrogenesis.
Methods:
Five hundred and seventy-three periosteal explants were harvested from forty-six two-month-old male New Zealand White rabbits. Explants were exposed to 50 or 100 ng/mL of TGF-beta1 for thirty or sixty minutes. The amount of cartilage formed was then determined with use of a standardized six-week agarose culture assay.
Results:
There was a significant increase in the amount of cartilage formation (p < 0.01), Type-II collagen content (p < 0.05), and sulfate incorporation (p < 0.0001) in explants treated with TGF-beta1. Maximal stimulation occurred following exposure to 100 ng/mL of TGF-beta1 for thirty minutes. There was also an increase in chondrocyte proliferation as measured by [ (3) H-] thymidine incorporation on day 5 of culture (p < 0.049).
Conclusions:
The findings of this study indicate that exposure to TGF-beta1 has a stimulatory effect on periosteal chondrogenesis. This stimulatory effect is observed even with a very brief exposure time of thirty minutes.
Clinical Relevance:
A possible clinical application of these findings is exposure of periosteal grafts that are currently utilized clinically to resurface articular defects to TGF-beta1 during the short time between graft procurement and implantation into the joint. This may obviate the need for intra-articular administration of TGF-beta1 and may enhance the ultimate graft incorporation and quality of cartilage repair.
