Effect of cartilage-derived factor on DNA and protein synthesis in cultured rat calvariae

Cartilage-derived factor (CDF), a peptide closely related to the somatomedins, was studied for its effects on bone formation by examining the synthesis of DNA, collagen, and noncollagen protein in 24-96 h cultures of 21-day fetal rat calvariae. After 24 h of treatment, CDF at concentrations of 0.3-30 micrograms/ml caused a dose-dependent stimulation of the incorporation of 3H-thymidine into DNA by 12-59%. The effect appeared and was maximal after 12 h, and was sustained for 96 h. CDF also increased the bone DNA content by 30-60%. After 24 h of treatment, CDF at 10-30 micrograms/ml had a small stimulatory effect on the incorporation of 3H-proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP). The effect on the labeling of CDP and NCP was sustained for 96 h. Cortisol decreased the stimulatory effect of CDF on DNA labeling but cortisol and CDF had an additive effect on the incorporation of 3H-proline into CDP. The CDF stimulatory effect on the labeling of DNA, CDP, and NCP was seen in both the periosteum and periosteum-free calvaria. These studies indicate that CDF stimulates bone DNA, collagen, and noncollagen protein synthesis in vitro and may be a local regulator of bone growth.