IL-4, but not vitamin D3, induces monoblastic cell line UG3 to differentiate into multinucleated giant cells on osteoclast lineage
✍ Scribed by Yoshio Kaji; Kazuma Ikeda; Takashi Ikeda; Kimihiro Kawakami; Kazunori Sasaki; Masanori Shindo; Kiyohiko Hatake; Mine Harada; Kazuo Motoyoshi; Satoshi Mori; Hiromichi Norimatsu; Jiro Takahara
- Book ID
- 102654187
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 684 KB
- Volume
- 182
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
The formation of multinucleated giant cells (MGCs) from monocytes/macrophages is controlled by various cytokines, the roles of which are not fully understood. Both interleukin (IL)-4 and 1␣,25(OH) 2 vitamin D 3 (D 3 ) are known to induce MGC formation from monocytes/macrophages. D 3 is also known as a stimulator of osteoclast formation in the presence of stroma cells, and IL-4 as an inhibitor. Previously, we showed that IL-4-induced MGCs from monocytes/macrophages expressed tartrate resistant acid phosphatase (TRAP) activity and hydroxyapatite-resorptive activity in the presence of M-CSF without stroma cells. In this study, we examined the effects of D 3 and/or IL-4 on MGC formation and the characteristics of these MGCs using a monoblastic cell line (UG3), to elucidate the involvement of these factors in osteoclast development without stroma cells. D 3 -induced MGCs showed none of the markers of osteoclasts, such as TRAP activity, calcitonin receptor (cal-R) expression, hydroxyapatite-resorptive activity, and bone-resorptive activity. A low concentration of D 3 synergistically stimulated IL-4-induced TRAP-positive MGC formation, whereas a high concentration of D 3 inhibited it. When IL-4 was added on day 7 of the 2-week culture with D 3 , TRAP positivity reached maximum. On the other hand, delayed addition of D 3 on day 7 of culture did not increase the TRAP positivity. Although the fusion rate increased during the first week of the 2-week culture in the presence of D 3 , it increased further in the second week following the addition of IL-4 on day 7. Furthermore, IL-4-induced, or IL-4-and D 3 -induced MGCs differentiated into functional osteoclasts with bone-resorptive activity following coculture with osteoblastic cells, whereas D 3 -induced MGCs did not acquire bone-resorptive activity even after coculture with osteoblastic cells in the presence of D 3 . These findings suggest that IL-4 initiates osteoclast development of UG3 cells, although stroma cells were necessary for development of functional osteoclasts. On the other hand, D 3 had only a "supportive" effect on this differentiation. IL-4 and direct contact with stroma cells may regulate different stages in the multistep process of osteoclastogenesis of UG3 cells.