INVITRO RESPONSE OF NEONATAL CONDYLAR CARTILAGE TO SIMULTANEOUS EXPOSURE TO THE PARATHYROID-HORMONE FRAGMENTS 1-34, 28-48, AND 53-84 HPTH

Mandibular condylar explants of neonatal ICR mice were maintained as serum-free organ culture systems and were used to study the effects of three synthetic fragments of human parathyroid hormone (hPTH) on the morphology of the organ and its ability to incorporate [H-3]thymidine. Forty-eight-hour incubation with hPTH (1-34), at a concentration of 0.5-mu-g/ml caused an increase of 88% in DNA synthesis and a marked increase in the size of the chondroprogenitor zone. The mitogenic effect of hPTH (1-34) was decreased to 34% over control levels when the fragment hPTH (28-48) was added to the system. However, the addition of the latter fragment brought about a marked enhancement in the mineralization of the cartilaginous extracellular matrix along with the formation of an appreciable amount of new bone. The de novo osseous tissue was attached to the mineralized cartilage. When the carboxyl-terminal fragment hPTH (53-84) was added together with the other two fragments, the mitogenic effect of hPTH (1-34) was completely abolished and the respective cultures incorporated [H-3]thymidine even less than untreated control cultures. Moreover, the addition of hPTH (53-84) to the culture system led to distinct structural features throughout the mineralized hypertrophic cartilage. The latter contained a mixture of cells within an unorganized extracellular matrix. Untreated control cultures lacked such structures, but contained the various cell zones as normally seen in neonatal condylar cartilage. Therefore, it seems reasonable to suggest that each of the three fragments tested induces a biological effect on neonatal cartilage and might be involved in the normal process of endochondral ossification.