title: Inhibition of osteoclast differentiation by overexpression of NDRG2 in monocytes.
abstract: N-Myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family of differentiation-related genes, has been characterized as a regulator of dendritic cell differentiation from monocytes, CD34(+) progenitor cells, and myelomonocytic leukemic cells. In this study, we show that NDRG2 overexpression inhibits the differentiation of U937 cells into osteoclasts in response to stimulation with a combination of macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of NF-κB ligand (RANKL). U937 cells stably expressing NDRG2 are unable to differentiate into multinucleated osteoclast-like cells and display reduced tartrate-resistant acid phosphatase (TRAP) activity and resorption pit formation. Furthermore, NDRG2 expression significantly suppresses the expression of genes that are crucial for the proliferation, survival, differentiation, and function of osteoclasts, including c-Fos, Atp6v0d2, RANK, and OSCAR. The activation of ERK1/2 and p38 is also inhibited by NDRG2 expression during osteoclastogenesis, and the inhibition of osteoclastogenesis by NDRG2 correlates with the down-regulation of the expression of the transcription factor PU.1. Taken together, our results suggest that the expression of NDRG2 potentially inhibits osteoclast differentiation and plays a role in modulating the signal transduction pathway responsible for osteoclastogenesis.
authors.affiliation: Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Kyeongah
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Sorim
authors.initials: S
authors.lastname: Nam
authors.affiliation: Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences and the Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea. Electronic address: jslim@sookmyung.ac.kr.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C485172:Ndr2 protein, mouse
keywords: NDRG2; Osteoclastic cytokines; Osteoclastogenesis; U937 cells