KMUP-1 Suppresses RANKL-Induced Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss: Roles of MAPKs, Akt, NF-κB and Calcium/Calcineurin/NFATc1 Pathways

PLoS ONE

Volumn 8, Issue 7, 2013, Pages

  Liou, Shu Fen ^a   Hsu, Jong Hau ^b,c   Lin, I Ling ^d   Ho, Mei Ling ^e   Hsu, Pei Chuan ^e   Chen, Li Wen ^e   Chen, Ing Jun ^e   Yeh, Jwu Lai ^e  

^a CHIA NAN UNIVERSITY OF PHARMACY AND SCIENCE   (Taiwan)

^b KAOHSIUNG MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^c KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

^d KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

^e KAOHSIUNG MEDICAL UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

7 [2 [4 (2 CHLOROPHENYL)PIPERAZINYL]ETHYL] 1,3 DIMETHYLXANTHINE; ALKALINE PHOSPHATASE; CALCIUM; CATHEPSIN K; GELATINASE B; HIGH MOBILITY GROUP B1 PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; KT 5823; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; N [2 (4 BROMOCINNAMYLAMINO)ETHYL] 5 ISOQUINOLINESULFONAMIDE; OSTEOCALCIN; OSTEOCLAST DIFFERENTIATION FACTOR; PROTEIN C FOS; PROTEIN KINASE B; THROMBIN RECEPTOR ACTIVATING PEPTIDE; TRANSCRIPTION FACTOR FRA 1; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NFATC1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; XANTHINE DERIVATIVE;

ALKALINE PHOSPHATASE BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BONE DISEASE; BONE MINERAL; CONTROLLED STUDY; DRUG MECHANISM; FEMALE; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; OSTEOCLASTOGENESIS; OSTEOLYSIS; OVARIECTOMY; PROTEIN BLOOD LEVEL; SIGNAL TRANSDUCTION;

ANIMALS; BONE DENSITY; BONE DENSITY CONSERVATION AGENTS; CALCINEURIN; CALCIUM; CYCLIC AMP; CYCLIC GMP; FEMALE; GENE EXPRESSION REGULATION; HUMANS; MICE; MICE, INBRED BALB C; MITOGEN-ACTIVATED PROTEIN KINASES; NF-KAPPA B; NFATC TRANSCRIPTION FACTORS; OSTEOCLASTS; OSTEOPOROSIS; OVARIECTOMY; PIPERIDINES; PROTO-ONCOGENE PROTEINS C-AKT; RANK LIGAND; SIGNAL TRANSDUCTION; XANTHINES;

EID: 84880769055     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0069468     Document Type: Article

References (41)

1. Boyle WJ, Simonet WS, Lacey DL, (2003) Osteoclast differentiation and activation. Nature 423: 337-342.
2. Teitelbaum SL, (2000) Bone resorption by osteoclasts. Science 289: 1504-1508.
3. Tintut Y, Parhami F, Tsingotjidou A, Tetradis S, Territo M, et al. (2002) 8-Isoprostaglandin E2 enhances receptor-activated NFκB ligand (RANKL)-dependent osteoclastic potential of marrow hematopoietic precursors via the cAMP pathway. J Biol Chem 277: 14221-14226.
4. Essayan DM, (2001) Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 108: 671-680.
5. Soderling SH, Bayuga SJ, Beavo JA, (1998) Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase. Proc Natl Acad Sci USA 95: 8991-8996.
6. Kinoshita T, Kobayashi S, Ebara S, Yoshimura Y, Horiuchi H, et al. (2000) Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice. Bone 27: 811-817.
7. Tsutsumimoto T, Wakabayashi S, Kinoshita T, Horiuchi H, Takaoka K, (2002) A phosphodiesterase inhibitor, pentoxifylline, enhances the bone morphogenetic protein-4 (BMP-4)-dependent differentiation of osteoprogenitor cells. Bone 31: 396-401.
8. Yamagami H, Nishioka T, Ochiai E, Fukushima K, Nomura M, et al. (2003) Inhibition of osteoclastogenesis by a phosphodiesterase 4 inhibitor XT-611 through synergistic action with endogenous prostaglandin E2. Biochem Pharmacol 66: 801-807.
9. Waki Y, Horita T, Miyamoto K, Ohya K, Kasugai S, (1999) Effects of XT-44, a phosphodiesterase 4 inhibitor, in osteoblastgenesis and osteoclastgenesis in culture and its therapeutic effects in rat osteopenia models. Jpn J Pharmacol 79: 477-483.
10. Holliday LS, Dean AD, Lin RH, Greenwald JE, Gluck SL, (1997) Low NO concentrations inhibit osteoclast formation in mouse marrow cultures by cGMP-dependent mechanism. Am J Physiol 272: F283-F291.
11. Armstrong AP, Tometsko ME, Glaccum M, Sutherland CL, Cosman D, et al. (2002) A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function. J Biol Chem 277: 44347-44356.
12. Wada T, Nakashima T, Hiroshi N, Penninger JM, (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12: 17-25.
13. Koga T, Inui M, Inoue K, Kim S, Suematsu A, et al. (2004) Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 428: 758-763.
14. Wu BN, Lin RJ, Lin CY, Shen KP, Chiang LC, et al. (2001) A xanthine-based KMUP-1 with cyclic GMP enhancing and K(+) channels opening activities in rat aortic smooth muscle. Br J Pharmacol 34: 265-274.
15. Lin RJ, Wu BN, Lo YC, Shen KP, Lin YT, et al. (2002) KMUP-1 relaxes rabbit corpus cavernosum smooth muscle in vitro and in vivo: involvement of cyclic GMP and K(+) channels. Br J Pharmacol 135: 1159-1166.
16. Wu BN, Lin RJ, Lo YC, Shen KP, Wang CC, et al. (2004) KMUP-1, a xanthine derivative, induces relaxation of guinea-pig isolated trachea: the role of the epithelium, cyclic nucleotides and K+ channels. Br J Pharmacol 142: 1105-1114.
17. Wu BN, Chen CW, Liou SF, Yeh JL, Chung HH, et al. (2006) Inhibition of proinflammatory tumor necrosis factor-{alpha}-induced inducible nitric-oxide synthase by xanthine-based 7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) and 7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1, 3-dimethylxanthine (KMUP-3) in rat trachea: The involvement of soluble guanylate cyclase and protein kinase G. Mol Pharmacol. 70: 977-985.
18. Liu CM, Lo YC, Wu BN, Wu WJ, Chou YH, et al. (2007) cGMP-enhancing- and alpha1A/alpha1D-adrenoceptor blockade-derived inhibition of Rho-kinase by KMUP-1 provides optimal prostate relaxation and epithelial cell anti-proliferation efficacy. Prostate 67: 1397-1410.
19. Liu CM, Lo YC, Tai MH, Wu BN, Wu WJ, et al. (2009) Piperazine-designed alpha 1A/alpha 1D-adrenoceptor blocker KMUP-1 and doxazosin provide down-regulation of androgen receptor and PSA in prostatic LNCaP cells growth and specifically in xenografts. Prostate 69: 610-623.
20. Yeh JL, Hsu JH, Wu PJ, Liou SF, Liu CP, et al. (2010) KMUP-1 attenuates isoprenaline-induced cardiac hypertrophy in rats through NO/cGMP/PKG and ERK1/2/calcineurin A pathways. Br J Pharmacol 159: 1151-1160.
21. Hsu YY, Liu CM, Tsai HH, Jong YJ, Chen IJ, et al. (2010) KMUP-1 attenuates serum deprivation-induced neurotoxicity in SH-SY5Y cells: roles of PKG, PI3K/Akt and Bcl-2/Bax pathways. Toxicology 268: 46-54.
22. Yeh JL, Hsu JH, Liang JC, Chen IJ, Liou SF, (2013) Lercanidipine and labedipinedilol-A attenuate lipopolysaccharide/interferon-γ-induced inflammation in rat vascular smooth muscle cells through inhibition of HMGB1 release and MMP-2, 9 activities. Atherosclerosis 226: 364-372.
23. Takatsuna H, Asagiri M, Kubota T, Oka K, Osada T, et al. (2005) Inhibition of RANKL-induced osteoclastogenesis by (-)-DHMEQ, a novel NF-kappaB inhibitor, through downregulation of NFATc1. J Bone Miner Res 20: 653-662.
24. Wu X, Li Z, Yang Z, Zheng C, Jing J, et al. (2012) Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-κB ligand-induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase/activator protein 1 and Ca2+-nuclear factor of activated T-cells cytoplasmic 1 signaling pathways. J Bone Miner Res 27: 1298-1308.
25. Zhou Z, Han JY, Xi CX, Xie JX, Feng X, et al. (2008) HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. J Bone Miner Res 23: 1084-1096.
26. Wang ZQ, Ovitt C, Grigoriadis AE, Möhle-Steinlein U, Rüther U, et al. (1992) Bone and haematopoietic defects in mice lacking c-fos. Nature 360: 741-745.
27. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, et al. (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3: 889-901.
28. Kwak HB, Lee BK, Oh J, Yeon JT, Choi SW, et al. (2010) Inhibition of osteoclast differentiation and bone resorption by rotenone, through down-regulation of RANKL-induced c-Fos and NFATc1 expression. Bone 46: 724-731.
29. Kim HH, Chung WJ, Lee SW, Chung PJ, You JW, et al. (2003) Association of sustained ERK activity with integrin 133 induction during receptor activator of nuclear factor kappaB ligand (RANKL)-directed osteoclast differentiation. Exp Cell Res 289: 368-377.
30. Braun T, Schett G, (2012) Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep 10: 101-108.
31. Hong MH, Williams H, Jin CH, Pike JW, (2000) The inhibitory effect of interleukin-10 on mouse osteoclast formation involves novel tyrosine-phosphorylated proteins. J Bone Miner Res 15: 911-918.
32. Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, Rovere- Querini P, (2005) HMGB1: Guiding immunity from within. Trends Immunol 26: 381-387.
33. Engsig MT, Chen QJ, Vu TH, Pedersen AC, Therkidsen B, et al. (2000) Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones. J Cell Biol 151: 879-889.
34. Roodman GD, (1999) Cell biology of the osteoclast. Exp Hematol 27: 1229-1241.
35. Lee SE, Woo KM, Kim SY, Kim HM, Kwack K, et al. (2002) The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone 30: 71-77.
36. Lee ZH, Kim HH, (2003) Signal transduction by receptor activator of nuclear factor κB in osteoclasts. Biochem Biophys Res Commun 305: 211-214.
37. Mediero A, Perez-Aso M, Cronstein BN (2013) Activation of Adenosine A2A receptor reduces osteoclast formation via PKA- and ERK1/2-mediated suppression of NFκB nuclear translocation. Br J Pharmacol May 3. doi: 10.1111/bph.12227. [Epub ahead of print].
38. Takimoto E, Champion HC, Li M, Belardi D, Ren S, et al. (2005) Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11: 214-222.
39. Kim YY, Kim SH, Oh SR, Sul OJ, Lee HY, et al. (2010) Increased fat due to estrogen deficiency induces bone loss by elevating monocytes chemoattractant protein-1 (MCP-1) production. Mol Cells 29: 277-282.
40. Szulc P, Delmas PD, (2001) Biochemical markers of bone turnover in men. Calcif Tissue Int 69: 229-234.
41. Bahlous A, Kalai E, Hadj Salah M, Bouzid K, Zerelli L, (2006) Biochemical markers of bone remodeling: recent data of their applications in managing postmenopausal osteoporosis. Tunis Med 84: 751-757.