Regulation of DNA Synthesis in Chick Calvaria Cells by Factors from Bone Organ Culture

Publisher Website
Google Scholar
Abstract
Embryonic chick bones growing in organ culture release a substance into the culture medium which stimulates bone formation in previously untreated bones. This conditioned medium also enhances proliferation of monolayer cultures of chick calvaria cells in serum-free medium. The active principle is nondialyzable, indicating a MW greater than 12,000 daltons. Dialysis also separates the mitogenic activity from a low-MW inhibitor. The amount of the mitogen found in conditioned medium increases as the rate of bone resorption increases in response to treatment with parathyroid hormone or 1,25-dihydroxyvitamin D3. Maximal stimulation of DNA synthesis in calvaria cells is evident with conditioned medium obtained 3-5 days after treatment of bone cultures with parathyroid hormone. The cells must be treated with the conditioned medium continuously for 20 h to obtain peak enhancement of DNA synthesis; there is no detectable effect in the first 8 h. The inhibitor acts within 4 h. The stimulatory factor evidently acts to increase cell proliferation by promoting entry of cells into the S phase of mitosis. This stimulator is a locally produced regulator of bone formation, probably acting via an increased proliferation in osteoblast precursor cells.