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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.4
- 수록면
- 316 - 321 (6page)
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초록· 키워드
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The receptor activator of nuclear factor κB (RANK) and its ligand RANKL are key regulators of osteoclastogenesis and well-recognized targets in developing treatments for bone disorders associated with excessive bone resorption, such as osteoporosis. Our previous work on the structure of the RANK-RANKL complex revealed that Loop3 of RANK, specifically the non-canonical disulfide bond at the tip, performs a crucial role in specific recognition of RANKL. It also demonstrated that peptide mimics of Loop3 were capable of interfering with the function of RANKL in osteoclastogenesis. Here, we reported the structure-based design of a smaller peptide with enhanced inhibitory efficiency. The kinetic analysis and osteoclast differentiation assay showed that in addition to the sharp turn induced by the disulfide bond, two consecutive arginine residues were also important for binding to RANKL and inhibiting osteoclastogenesis. Docking and molecular dynamics simulations proposed the binding mode of the peptide to the RANKL trimer, showing that the arginine residues provide electrostatic interactions with RANKL and contribute to stabilizing the complex. These findings provided useful information for the rational design of therapeutics for bone diseases associated with RANK/RANKL function.
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참고문헌 (22)
참고문헌 신청
Burgess, T. L. / 1999 / The ligand for osteoprotegerin(OPGL)directly activates mature osteoclasts / J. Cell Biol 145:527~538
Cohen, S. B. / 2008 / Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis : a twelve-month, multicenter, randomized, double-blind, placebocontrolled, phase II clinical trial / Arthritis Rheumatism 58:1299~1309
Cummings, S. R. / 2009 / Denosumab for prevention of fractures in postmenopausal women with osteoporosis / N Y J. Med 361:756~765
Dempster, D. W. / 2012 / Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis : a review of preclinical and clinical data / Clin. Ther 34:521~536
Denizot, F. / 1986 / Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability / J. Immunol. Methods 89:271~277
Cohen, S. B. / 2008 / Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis : a twelve-month, multicenter, randomized, double-blind, placebocontrolled, phase II clinical trial / Arthritis Rheumatism 58:1299~1309
Cummings, S. R. / 2009 / Denosumab for prevention of fractures in postmenopausal women with osteoporosis / N Y J. Med 361:756~765
Dempster, D. W. / 2012 / Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis : a review of preclinical and clinical data / Clin. Ther 34:521~536
Denizot, F. / 1986 / Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability / J. Immunol. Methods 89:271~277
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