Effect of Protein Kinase C Modulators on the Osteoclast-like Cell Generation Induced by Osteotropic Hormones

Abstract

Protein kinase C (PKC) has been known to play an important role in the prcress of cell differentiation. The present study was undertaken to in investigate the effect of modulators of PKC in the generation of osteoclast-like cells from mouse bone marrow cells. The marrow cells were collected from the femurs and tibiae 4- to 6-week-old mice and cultured for 8 days. In order to examine the role of PKC in the generation of osteoclast-like cells induced by hormones, a PKC modulator, PMA or H7 was sypplemented in the presence of PGE_(2), 1,25-dihydroxyvitamin D_(3), or PTH, After culture, the cells were stained for tartrate-resitant acid phosphatase (TRACP), a marker enzyme of osteoclast anld the TRACP-positive multinucleated cells (MNCs) which haue 3 or more nuclei were counted. The present study showed that TRACP positve MNCs were not formed in the presence of PMA and H7 alone. However, the generation of TRACP-positive MNCs induced by PGE_(2) and 1,25-dlhydroxroxyvltamin D_(3) was stimulated by PMA at 10^(-9)-10^(-7) M. this augmentation of TRACP-positive MNC generation was inhibited by the presence of 10^(-5) M H7. the generation of TRACP-positive MNCs induced by PTH was suppressed by 10^(-9)-10^(-7) M PMA. This suppression of TRACP-positivw MNC generation. These results suggest that PKC may play an important role in the generation of osteoclasis and may modulate the action of osteotropic hormones in the bone resorption.