Multiplication-Stimulating Activity (MSA) and Cartilage-Derived Factor (CDF): Biological Actions in Cultured Chondrocytes1

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Abstract
Previously, we showed that a polypeptide isolated from fetal bovine cartilage stimulates proteoglycan synthesis, RNA synthesis, and DNA synthesis in cultured rabbit costal chondrocytes. In the present study, the effects of the cartilage-derived factor (CDF) were compared with those of multiplication-stimulating activity (MSA), which is thought to be included in somatomedins. CDF and MSA markedly increased [2H]thymidine incorporation into rabbit costal chondrocytes from 7–14 h after their additions. The incorporation of [2H]uridine was also increased within 1–2 h in the cells incubated with the peptides. These stimulations of nucleic acid syntheses were followed by cell division in serum-free culture medium. On the other hand, the peptides enhanced the synthesis of sulfated proteoglycans within 7 h. Furthermore, the extent of stimulation of proteoglycan synthesis, as measured in terms of increased incorporation of [35S]sulfate, or [3H]serine into material precipitated with cetylpyridinium chloride, was consistently higher than the extent of CDF or MSA stimulation of total protein synthesis, as measured in terms of increased incorporation of [3H]serine into acid-insoluble cellular material. These findings suggest that the stimulation of proteoglycan synthesis by CDF and MSA is not directly linked to the peptide-induced stimulation of cell proliferation. The present study also showed that CDF is as effective as MSA in stimulating various metabolic indices in cultured chondrocytes at their optimal concentrations.

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