Parathyroid hormone increases the number of tartrate-resistant acid phosphatase-positive cells through prostaglandin E2 synthesis in adherent cell culture of neonatal rat bones.

Tartrate-resistant acid phosphatase (TRAP) is expressed during one of the steps of osteoclast differentiation. The involvement of prostaglandin E2 (PGE2) synthesis in PTH-induced increases in TRAP-positive cell number was studied in an improved slowly adhering cell culture system, prepared by removing preexisting osteoclasts from disaggregated bone cells obtained from 6-day-old rats. The majority of the TRAP-positive cells that appeared were mononuclear. In 1-day culture, PTH (0.025-0.25 nM) and PGE2 (1 microM) increased the number of mono- and multinucleated TRAP-positive cells. Indomethacin (50 microM) inhibited PTH-induced increase, and the inhibition was significantly abolished by the addition of PGE2. SC-19220, a specific antagonist for one class of PGE2 receptor, inhibited the increase induced by PTH and PGE2. PTH significantly stimulated the production of PGE2 in the culture. Peroxides, which are produced as byproducts of PGE2 biosynthesis, were detected in the adherent cells using dichlorofluorescene and increased the number of TRAP-positive cells. Small resorption pits were recognized on the surfaces of bone slices on which slowly adhering cells had been incubated for 3 days with PTH. These findings showed that PTH, through its effects on PGE2 synthesis and the subsequent reactions, induced the step at which TRAP is expressed, possibly during the differentiation of osteoclasts.