MicroRNA-26a Regulates RANKL-Induced Osteoclast Formation

다국어 초록 (Multilingual Abstract)

Osteoclasts are unique cells responsible for the resorption of bone matrix. MicroRNAs (miRNAs) are involved in the regulation of a wide range of physiological processes. Here, we examined the role of miR-26a in RANKL-induced osteoclastogenesis. The expression of miR-26a was upregulated by RANKL at the late stage of osteoclastogenesis.
Ectopic expression of an miR-26a mimic in osteoclast precursor cells attenuated osteoclast formation, actin-ring formation, and bone resorption by suppressing the expression of connective tissue growth factor/CCN family 2 (CTGF/ CCN2), which can promote osteoclast formation via upregulation of dendritic cell-specific transmembrane protein (DC-STAMP). On the other hand, overexpression of miR-26a inhibitor enhanced RANKL-induced osteoclast formation and function as well as CTGF expression. In addition, the inhibitory effect of miR-26a on osteoclast formation and function was prevented by treatment with recombinant CTGF. Collectively, our results suggest that miR-26a modulates osteoclast formation and function through the regulation of CTGF.

참고문헌 (Reference)

1 Lee, S. H., "v-ATPase V0subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation" 12 : 1403-1409, 2006

2 Rossi, M., "miR-29b negatively regulates human osteoclastic cell differentiation and function : implications for the treatment of multiple myeloma-related bone disease" 228 : 1506-1515, 2013

3 Cheng, P., "miR-148a regulates osteoclastogenesis by targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B" 28 : 1180-1190, 2013

4 Asagiri, M., "The molecular understanding of osteoclast differentiation" 40 : 251-264, 2007

5 Ambros, V., "The functions of animal microRNAs" 431 : 350-355, 2004

6 Miyauchi, Y., "The Blimp1-Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis" 207 : 751-762, 2010

7 윤방웅, "SLAT Negatively Regulates RANKL-Induced Osteoclast Differentiation" 한국분자세포생물학회 36 (36): 252-257, 2013

8 Miyamoto, T., "Regulators of osteoclast differentiation and cell-cell fusion" 60 : 101-105, 2011

9 Kim, J. H., "RANKL induces NFATc1 acetylation and stability via histone acetyltransferases during osteoclast differentiation" 436 : 253-262, 2011

10 Walsh, M. C., "Osteoimmunology: interplay between the immune system and bone metabolism" 24 : 33-63, 2006

11 Luzi, E., "Osteogenic differentiation of human adipose tissuederived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor" 23 : 287-295, 2008

12 Boyle, W. J., "Osteoclast differentiation and activation" 423 : 337-342, 2003

13 Wei, C., "NF-kappaB mediated miR-26a regulation in cardiac fibrosis" 228 : 1433-1442, 2013

14 Bartel, D. P., "MicroRNAs : genomics, biogenesis, mechanism, and function" 116 : 281-297, 2004

15 Wong, C. F., "MicroRNA-26a targets the histone methyltransferase enhancer of zeste homolog 2 during myogenesis" 283 : 9836-9843, 2008

16 Lee, Y., "MicroRNA-124 regulates osteoclast differentiation" 56 : 383-389, 2013

17 Kim, K., "MafB negatively regulates RANKL-mediated osteoclast differentiation" 109 : 3253-3259, 2007

18 Zhang, J., "Interferon-beta-induced miR-155 inhibits osteoclast differentiation by targeting SOCS1 and MITF" 586 : 3255-3262, 2012

19 Zhao, B., "Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis" 15 : 1066-1071, 2009

20 Danks, L., "Immunology and bone" 154 : 29-39, 2013

21 Zhou, J., "Down-regulation of microRNA-26a promotes mouse hepatocyte proliferation during liver regeneration" 7 : 33577-, 2012

22 Yagi, M., "DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells" 202 : 345-351, 2005

23 Nozawa, K., "Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis" 11 : 174-, 2009

24 Takigawa, M., "CCN2 : a master regulator of the genesis of bone and cartilage" 7 : 191-201, 2013

25 Nishida, T., "CCN family 2/connective tissue growth factor(CCN2/CTGF)promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein(DC-STAMP)" 26 : 351-363, 2011