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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.3
- 수록면
- 279 - 284 (6page)
- DOI
- 10.14348/molcells.2015.2340
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초록· 키워드
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Obatoclax, a pan-Bcl2 inhibitor, shows antitumor activities in various solid malignancies. Bcl2-deficient mice have shown the importance of Bcl2 in osteoclasts, as the bone mass of the mice was increased by the induced apoptosis of osteoclasts. Despite the importance of Bcl2, the effects of obatoclax on the proliferation and differentiation of osteoclast precursors have not been studied extensively.
Here, we describe the anti-proliferative effects of obatoclax on osteoclast precursors and its negative role on fusion of the cells. Stimulation with low doses of obatoclax significantly suppressed the proliferation of osteoclast precursors in a dose-dependent manner while the apoptosis was markedly increased. Its stimulation was sufficient to block the activation of ERK MAP kinase by RANKL. The same was true when PD98059, an ERK inhibitor, was administered to osteoclast precursors. The activation of JNK1/2 and p38 MAP kinase, necessary for osteoclast differentiation, by RANKL was not affected by obatoclax. Interestingly, whereas the number of TRAP-positive mononuclear cells was increased by both obatoclax and PD98059, fused, multinucleated cells larger than 100 m in diameter containing more than 20 nuclei were completely reduced.
Consistently, obatoclax failed to regulate the expression of osteoclast marker genes, including c-Fos, TRAP, RANK and CtsK. Instead, the expression of DC-STAMP and Atp6v0d2, genes that regulate osteoclast fusion, by RANKL was significantly abrogated by both obatoclax and PD98059. Taken together, these results suggest that obatoclax down-regulates the proliferation and fusion of osteoclast precursors through the inhibition of the ERK1/2 MAP kinase pathway.
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참고문헌 (36)
참고문헌 신청
Anderson, D. M. / 1997 / A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function / Nature 390:175~179
Blair, H. C. / 1998 / How the osteoclast degrades bone / Bioessays 20:837~848
Boyle, W. J. / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
Campas, C. / 2006 / Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells / Exp. Hematol 34:1663~1669
Choi, J. / 2013 / Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DCSTAMP/CtsK and TRAP pathway / Cell. Signal 25:1222~1227
Blair, H. C. / 1998 / How the osteoclast degrades bone / Bioessays 20:837~848
Boyle, W. J. / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
Campas, C. / 2006 / Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells / Exp. Hematol 34:1663~1669
Choi, J. / 2013 / Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DCSTAMP/CtsK and TRAP pathway / Cell. Signal 25:1222~1227
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