Mol. Cells 2019; 42(2): 183~188
Calcium-Phosphate Crystals Promote RANKL Expression via the Downregulation of DUSP1
YunJeong Choi1, Ji Hyun Yoo1, Youngkyun Lee2, Moon Kyoung Bae1, and Hyung Joon Kim1,*
1Department of Oral Physiology, BK21 PLUS Project, and Institute of Translational Dental Sciences, School of Dentistry, Pusan National University, Yangsan, Korea, 2Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea
Received September 7, 2018; Revised October 24, 2018; Accepted January 2, 2019.; Published online January 24, 2019.
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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 osteoblastosteoclast coculture system that resembles in vivo osteoblastdependent 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.
Keywords: DUSP1, osteoarthritis, osteoclastogenesis, RANKL

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