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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 183 - 188 (6page)
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Osteoarthritis (OA) is a naturally occurring, irreversible disorder and a major health burden. The disease is multifactorial, involving both physiological and mechanical processes, but calcium crystals have been associated intimately with its pathogenesis. This study tested the hypothesis that these crystals have a detrimental effect on the differentiation of osteoclasts and bone homeostasis. This study employed an osteoblast-osteoclast coculture system that resembles in vivo osteoblast-dependent osteoclast differentiation along with Ca2+-phosphate-coated culture dishes. The calcium-containing crystals upregulated the expression of RANKL and increased the differentiation of osteoclasts significantly as a result. On the other hand, osteoblast differentiation was unaffected. MicroRNA profiling showed that dual-specificity phosphatases 1 (DUSP1) was associated with the increased RANKL expression. DUSP1 belongs to a family of MAPK phosphatases and is known to inactivate all three groups of MAPKs, p38, JNK, and ERK. Furthermore, knockdown of DUSP1 gene expression suggested that RANKL expression increases significantly in the absence of DUSP1 regulation. Microarray analysis of the DUSP1 mRNA levels in patients with pathological bone diseases also showed that the downregulated DUSP1 expression leads to increased expression of RANKL and consequently to the destruction of the bone observed in these patients. These findings suggest that calcium-containing crystals may play a crucial role in promoting RANKL-induced osteoclastogenesis via DUSP1.
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참고문헌 (24)
참고문헌 신청
Boyle, W. J. / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
Brandt, K. / 1998 / Osteoarthritis / Oxford University Press :70~74
Burr, D. B. / 2003 / Microfractures and microcracks in subchondral bone : are they relevant to osteoarthrosis? Rheum / Dis. Clin. N. Am 29:675~685
Camps, M. / 2000 / Dual specificity phosphatases : a gene family for control of MAP kinase function / FASEB J 14:6~16
Corr, E. M. / 2017 / Osteoarthritis associated basic calcium phosphate crystals activate membrane proximal kinases in human innate immune cells / Arthritis Res. Ther 19:23
Brandt, K. / 1998 / Osteoarthritis / Oxford University Press :70~74
Burr, D. B. / 2003 / Microfractures and microcracks in subchondral bone : are they relevant to osteoarthrosis? Rheum / Dis. Clin. N. Am 29:675~685
Camps, M. / 2000 / Dual specificity phosphatases : a gene family for control of MAP kinase function / FASEB J 14:6~16
Corr, E. M. / 2017 / Osteoarthritis associated basic calcium phosphate crystals activate membrane proximal kinases in human innate immune cells / Arthritis Res. Ther 19:23
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