To examine the potential for rejuvenation of aged periosteum by local injection of transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) alone or in combination to induce cambium cell proliferation and enhance in vitro periosteal cartilage formation.
A total of 367 New Zealand white rabbits (6, 12, and 24+ month-old) received subperiosteal injections of TGF-beta1 and/or IGF-1 percutaneously. After 1, 3, 5, or 7 days, the rabbits were sacrificed and cambium cellularity or in vitro cartilage forming capacity was determined.
A significant increase in cambium cellularity and thickness, and in vitro cartilage formation was observed after injection of TGF-beta1 alone or in combination with IGF-1. In 12 month-old rabbits, mean cambium cellularity increased 5-fold from 49 to 237 cells/mm and in vitro cartilage production increased 12-fold from 0.8 to 9.7 mg 7 days after TGF-beta1 (200 ng) injection compared to vehicle controls (P<0.0001). A correlation was observed between cambium cellularity and in vitro cartilage production (R2=0.98). An added benefit of IGF-1 plus TGF-beta1 on in vitro cartilage production compared to TGF-beta1 alone was observed in the 2 year-old rabbits. IGF-1 alone generally had no effect on either cambium cellularity or in vitro cartilage production in any of the age groups.
These results clearly demonstrate that it is possible to increase cambium cellularity and in vitro cartilage production in aged rabbit periosteum, to levels comparable to younger rabbits, using local injection of TGF-beta1 alone or in combination with IGF-1, thereby rejuvenating aged periosteum.