In vitro effect of hormones and growth factors on the incorporation of [3H]leucine, [35S]sulfate and [3H]proline by chondrocytes of aging mice.
The ability of parathyroid hormone (PTH 1-84), dexamethasone, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and human transforming growth factor beta (hTGF-beta) to stimulate the synthesis of matrical components in articular cartilage of aging mice, was studied in an organ culture system. A marked age-dependent decrease was observed in the synthesis of sulfated glycosaminoglycans (GAGs), protein, collagen digestible protein (CDP) and non-collagen protein (NCP) between 1 and 18 months of age. The addition of hTGF-beta (1 ng/ml) into the culture medium resulted in a significant (P < 0.01) increase of both protein and sulfated GAGs in condylar cartilage from animals aged 1, 3, 6 and 12 months. PGE2 (10 micrograms/ml) induced [3H]leucine and [35S]SO4 incorporation into condylar cartilage from 1, 3 and 6 months old animals. A stimulatory effect of PGE1 (10 micrograms/ml) on [3H]leucine incorporation was noted at 1 and 3 months of age. The effect of PTH appeared to be stimulatory only for protein synthesis in young (1 and 3 months old) animals, whereas it had no effect at 6, 12 and 18 months of age. In contrast, dexamethasone exerted a stimulatory effect on young adults (6 months old) and in matured (12 months old) animals, respectively and a slight inhibitory effect on young (1 and 3 months old) animals. [3H]Proline incorporation was enhanced by all the factors tested in 1-month-old animals. In cultures from 6- and 18-month-old animals only PGE1 and PGE2 appeared to be stimulatory. It is concluded that synthesis of protein, sulfated GAGs and collagen by chondrocytes from maturing and osteoarthritic senescent animals can be stimulated by hormones and growth factors. The efficiency of this response, however, varied according to the animal's age and the factor studied.