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Protein arginine methylation is a novel form of posttranslational modification mediated by protein arginine methyltransferase (PRMTs). PRMT1, a major isoform of the PRMT family, is responsible for various biological functions, including cellular differentiation. Although the important function that PRMT1 plays in various tissues is being increasingly recognized, its role in receptor activation of NF-κB ligand (RANKL)-induced osteoclastogenesis or osteoporosis has not yet been described. Here, we show that PRMT1 is essential for RANKL-induced osteoclastogenesis in vitro and for bone loss in vivo. RANKL treatment increased the expression of PRMT1 and its nuclear localization in bone marrow-derived macrophages (BMDMs) in a c-Jun N-terminal kinase (JNK)-dependent manner. Silencing PRMT1 attenuated RANKL-induced osteoclastogenesis by decreasing tartrate-resistant acid phosphatase (TRAP)-positive cells and inhibiting F-actin ring formation and bone resorption, which was confirmed in a separate experiment using haploinsufficient cells from PRMT1+/- mice. Our results also revealed that PRMT1 regulates the transcription activity of NF-κB by directly interacting with it in RANKL-treated BMDMs. An in vivo study showed that the haploinsufficiency of PRMT1 reduced the enzyme activity of TRAP and increased the bone mineral density in the metaphysis of ovariectomized (OVX) mice. Finally, treatment with estrogen (E2) downregulated the RANKL-induced expression of PRMT1, suggesting that estrogen may exert an inhibitory effect on osteoclastogenesis by suppressing PRMT1 expression. Our results suggest that PRMT1 plays an important role in the progression of osteoporosis and that it might be a good therapeutic target for postmenopausal osteoporosis.

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참고문헌 (54건) : 자료제공( 네이버학술정보 )

참고문헌 목록에 대한 테이블로 번호, 참고문헌, 국회도서관 소장유무로 구성되어 있습니다.
번호 참고문헌 국회도서관 소장유무
1 The complexities of skeletal biology 네이버 미소장
2 Disturbed MEK/ERK signaling increases osteoclast activity via the Hedgehog-Gli pathway in postmenopausal osteoporosis 네이버 미소장
3 Perspective on post-menopausal osteoporosis: establishing an interdisciplinary understanding of the sequence of events from the molecular level to whole bone fractures. 네이버 미소장
4 Melton, L. J., Chrischilles, E. A., Cooper, C., Lane, A. W. & Riggs, B. L. How many women have osteoporosis? J. Bone Miner. Res. 20, 886-892 (2005). 미소장
5 Anderson, G. L. et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. J. Am. Med Assoc. 291, 1701-1712 (2004). 미소장
6 CSF-1 regulation of the wandering macrophage: complexity in action 네이버 미소장
7 Selective inhibition of RANK blocks osteoclast maturation and function and prevents bone loss in mice. 네이버 미소장
8 Osteoclast differentiation requires TAK1 and MKK6 for NFATc1 induction and NF-kappaB transactivation by RANKL. 네이버 미소장
9 Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. 네이버 미소장
10 MAP kinase signalling cascades and transcriptional regulation. 네이버 미소장
11 Chen, Y. et al. PRMT-1 and DDAHs-induced ADMA upregulation is involved in ROS- and RAS-mediated diabetic retinopathy. Exp. Eye Res. 89, 1028-1034 (2009). 미소장
12 Arginine methylation of the histone H3 tail impedes effector binding. 네이버 미소장
13 Yang, Y. & Bedford, M. T. Protein arginine methyltransferases and cancer. Nat. Rev. Cancer 13, 37-50 (2013). 미소장
14 Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3. 네이버 미소장
15 Kim, D. I. et al. PRMT1 and PRMT4 regulate oxidative stress-induced retinal pigment epithelial cell damage in SIRT1-dependent and SIRT1-independent manners. Oxid. Med. Cell Longev. 2015, 617919 (2015). 미소장
16 Mathioudaki, K. et al. The PRMT1 gene expression pattern in colon cancer. Br. J. Cancer 99, 2094-2099 (2008). 미소장
17 Thioredoxin-interacting protein mediates hepatic lipogenesis and inflammation via PRMT1 and PGC-1α regulation in vitro and in vivo 네이버 미소장
18 The clinical significance of asymmetric dimethylarginine. 네이버 미소장
19 Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA 네이버 미소장
20 Effect of age on bone mineral density and the serum concentration of endogenous nitric oxide synthase inhibitors in rats. 네이버 미소장
21 Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine. 네이버 미소장
22 Kemeny-Beke, A. et al. Increased production of asymmetric dimethylarginine (ADMA) in ankylosing spondylitis: association with other clinical and laboratory parameters. Jt. Bone Spine 78, 184-187 (2011). 미소장
23 Biochemistry and regulation of the protein arginine methyltransferases (PRMTs). 네이버 미소장
24 Inhibition of PRMT5 suppresses osteoclast differentiation and partially protects against ovariectomy-induced bone loss through downregulation of CXCL10 and RSAD2 네이버 미소장
25 Cathepsin K inhibitors: a novel target for osteoporosis therapy. 네이버 미소장
26 RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice. 네이버 미소장
27 Amiloride inhibits osteoclastogenesis by suppressing nuclear factor-κB and mitogen-activated protein kinase activity in receptor activator of nuclear factor-κB-induced RAW264.7 cells. 네이버 미소장
28 Protein Arginine Methyltransferase 1 Coactivates NF-κB-Dependent Gene Expression Synergistically with CARM1 and PARP1 네이버 미소장
29 Endocrinology Reviewers, 2014 네이버 미소장
30 Robinson, L. J. et al. Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-alpha with BCAR1 and Traf6. Exp. Cell Res. 315, 1287-1301 (2009). 미소장
31 Endocrinology Reviewers, 2009 네이버 미소장
32 Requirement for NF-κB in osteoclast and B-cell development 네이버 미소장
33 Transplantation: A simple test for PVN 네이버 미소장
34 Asymmetric dimethylarginine (ADMA) treatment induces apoptosis in cultured rat mesangial cells via endoplasmic reticulum stress activation 네이버 미소장
35 Dynamics of human protein arginine methyltransferase 1(PRMT1) in vivo. 네이버 미소장
36 Human protein arginine methyltransferases in vivo--distinct properties of eight canonical members of the PRMT family. 네이버 미소장
37 Lipotoxicity-Induced PRMT1 Exacerbates Mesangial Cell Apoptosis via Endoplasmic Reticulum Stress. 네이버 미소장
38 Methylation of Histone H4 at Arginine 3 Facilitating Transcriptional Activation by Nuclear Hormone Receptor 네이버 미소장
39 NF-kB functions in osteoclasts 네이버 미소장
40 Autoamplification of NFATc1 expression determines its essential role in bone homeostasis. 네이버 미소장
41 Osteoclast differentiation and activation 네이버 미소장
42 Takayanagi, H. et al. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev. Cell 3, 889-901 (2002). 미소장
43 Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. 네이버 미소장
44 Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts 네이버 미소장
45 Activation of p38 mitogen-activated protein kinase is crucial in osteoclastogenesis induced by tumor necrosis factor 네이버 미소장
46 Reciprocal role of ERK and NF-kappaB pathways in survival and activation of osteoclasts. 네이버 미소장
47 Activation of PRMT1 and PRMT5 mediates hypoxia- and ischemia-induced apoptosis in human lung epithelial cells and the lung of miniature pigs: The role of p38 and JNK mitogen-activated protein kinases 네이버 미소장
48 Regulation and function of the JNK subgroup of MAP kinases. 네이버 미소장
49 c-Fos: A Key Regulator of Osteoclast-Macrophage Lineage Determination and Bone Remodeling 네이버 미소장
50 The mechanisms of estrogen regulation of bone resorption. 네이버 미소장
51 Protein arginine methyltransferase 1 regulates hepatic glucose production in a FoxO1-dependent manner. 네이버 미소장
52 Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. 네이버 미소장
53 Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia 네이버 미소장
54 Determination of a reference value for N(G), N(G)-dimethyl-L-arginine in 500 subjects. 네이버 미소장

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