Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism.

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Abstract
An in vitro system, was developed using embryonic chicken tibiae grown in a serum-free medium, which exhibits simultaneous bone formation and resorption. Tibiae from 8 day embryos increased in mean (.+-.SD) length (4.0 .+-. 0.4 to 11.0 .+-. 0.3 mm) and dry wt (0.30 .+-. 0.04 to 0.84 .+-. 0.04 mg) during 12 days in vitro. There was increased incorporation of [3H]proline into hydroxyproline (120 .+-. 20 to 340 .+-. 20 cmp/mg of bone per 24 h) as a measure of collagen synthesis and a 62 .+-. 5% increase in total Ca and 45Ca taken up as an indication of active mineralization. A physiologic concentration (1 pM) of parathyroid hormone stimulated bone resorption over control levels in this system. Parathyroid hormone stimulated the release of [3H]hydroxyproline from the bone shafts but not from the cartilage ends, indicating the specificity of the response. With 1 pM parathyroid hormone an acute inhibition of bone formation was observed, followed (after 12-16 h) by a chronic stimulation of bone formation during the 12-day incubation. Both mineral uptake and matrix formation were enhanced at approximately the same rate during the 12 day incubation. The chronic enhancement of formation required parathyroid hormone only for the initial 8-10 h of incubation. These results could be explained by the production or release of a factor from bone to stimulate formation in response to the acute increase in resportion.sbd.a coupling factor. Dialyzed culture medium conditioned by actively resorbing bones stimulated bone formation over controls when added to organ cultures at a 1:20 dilution. The factor is larger than 12,000 daltons as determined by dialysis. The factor is specific for the bone shaft and did not affect the cartilage ends.