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KMID : 0438619940180020093
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Journal of Oral Biology
1994 Volume.18 No. 2 p.93 ~ p.102
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Modulating Effects of Transforming Growth Factor-β on the Osteoclast-like Cell Generation in Mouse Bone Marrow Cultures
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Kim, Gwan-Shik
Cheong, Dong-Kyun/Kim, Se-Won/Ko, Seong-Hee/Baek, Jeong-Hwa/Lee, Jong-Oh/Kim, Joong-Soo
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Abstract
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Transforming growth factor-β (TGF-β) is a multifunctional polypeptide with diverse effects on the proliferation, differentiation and other functions in a wide variety of cells. TGF-β is highly abundant in bone and is now recognized as an important growth regulator and modulator in bone metabolism, but its role in osteoclast differentiation remains controversial. The present study was ultdertaken to investigate the effects of TGF-β on osteoclast generation induced by prostaglandin E_(2), (PGE_(2)) or 1,25-dihydroxycholecalciferol (1,25-DHCC) in mouse bone marrow cultures. The number of osteoclast-like cells (OC-like cells) which retain osteoclastic characteristics, including multinuclearity and positive staining for tartrate-resistant acid phesphatase, was incrensed by PGE_(2) and 1.25-DHCC in dosodependent manner. OC-like cell formation in presence of 1,25-DHCC was partially inhibited by simultaneous addition of indomethacin, indicating the possible involvement of endogeneous PG in 1.25-DHCC-induced OC-like cell generation in mouse bone marrow cultures. TGF-β, by itself, failed to produce a significant effect on OC-like cell formation. In contrast, PGE_(2)- or 1,25-DHCC-induced generation of OC-like cells was markedly modulated by TGF-β treatment with different profiles. TGF-β reduced the number of OC-like cells formed in presence of PGE_(2) over the concentration range tested and atmost complete inhibition was seen at 1 ng/㎖. However, TCF-β produced a biphasic effect on OC-like cell generation induced by 1,25-DHCC; at low concentration stimulated, whereas at higher concentration suppressed the formation of OC-like cell. And further treatment of cultures with ir lomethacin significarltly blocked the stimulatory effect of TGF-β observed at low concentrations. In addition, effect of TGF-β appeared to be time-dependent rather than a generalized one during the whole culture period. TGF- effectively inhibited PGE_(2)-induced OC-like cell formation only when it was present at particular period of cultures. These findings suggest that TGF-β modulates various steps in cascade of osteoclast development and activation in different ways involving PG-mediated or PG-insensitive pathways.
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