YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effect of Pentoxifylline, a Phosphodiesterase Inhibitor, on Osteoclast Formation

Phosphodiesterase 저해제 Pentoxifylline이 파골세포 분화에 미치는 영향

  • 김민혜 (숙명여자대학교 약학대학) ;
  • 전윤나 (숙명여자대학교 약학대) ;
  • 임미정 (숙명여자대학교 약학대학)
  • Published : 2004.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

Phosphodiesterases (PDEs) are enzymes that degrade intracellular cAMP. In the present study, pentoxifylline, a PDE inhibitor, induced osteoclast formation in co-cultures of mouse bone marrow cells and calvarial osteoblasts. To address the involvement of the osteoclast differentiation factor TNF-related activation-induced cytokine (TRANCE, identical to RANKL, ODF, and OPGL), mouse bone marrow cells and calvarial osteoblasts were co-cultured with pentoxifylline in the presence of OPG, a decoy receptor for TRANCE. The osteoclastogenic effect of pentoxifylline was completely blocked by addition of OPG, suggesting that TRANCE is involved in the osteoclast formation induced by pentoxifylline, Northern blot analysis revealed that pentoxifylline significantly induced TRANCE mRNA expression in calvarial osteoblasts. These results suggests that pentoxifylline regulates TRANCE expression in osteoblasts, which in turn controls osteoclast formation.

Keywords

References

  1. Takahashi, N., Akatsu, T., Udagawa, N., Sasaki, T., Yamaguchi, A.,Moseley, J . M., Martin, T. J.and Suda, T. : Osteoblastic cells are involved in osteoclast formation. Endoctinology 123, 2600 (1988) https://doi.org/10.1210/endo-123-5-2600
  2. Suda, T.，Takahashi，N., Udagawa, N., Jimi, E., Gillespie, M. T and Martin, T. J. : Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr. Rev. 20, 345 (1999) https://doi.org/10.1210/er.20.3.345
  3. Wong, B. R., Rho, J., Arron, J., Robinson, E., Orlinick, J., Chao, M., Kalach S., Cayani, E., Bartlett, F. S. 3rd, Frankel， W. N., Lee, S. Y. and Choi, Y. : TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells. J. Biol. Chem. 272 , 25190 (1997) https://doi.org/10.1074/jbc.272.40.25190
  4. Yasuda, H., Shima，N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., Tsuda, E., Morinaga, T., Higashio, K., Udagawa, N., Takahashi, N. and Suda, T : Osteoclast differentiation factor is a ligand for steoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl. Acad. Sci. USA 95, 3597 (1998)
  5. Lacey, D. L., Timms, E., Tan, H. L., Kelley, M. J., Dunstan, C. R., Burgess , T., Elliott, R., Colombero, A., Elliott, G., Scully, S., Hsu,H., Sullivan, J., Hawkins, N., Davy, E., Capparelli, C., Eli, A., Qian, Y. X., Kaufman, S., Sarosi, I., Shalhoub, V.,Senaldi, G., Guo, J., Delaney, J. and Boyle, W.J. : Osteoprotegerin ligand is cytokine that regulates osteoclast differentiation and activation. Cell 93, 165 (1998) https://doi.org/10.1016/S0092-8674(00)81569-X
  6. Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M. S., Luthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., Shimamoto, G., DeRose, M., Elliott, R., Colombero, A., Tan, H. L., Trail, G., Sullivan, J., Davy, E., Bucay, N., Renshaw-Gegg, L., Hughes, T M., Hill, D., Pattison, W., Campbell, P. and Boyle, W. J. : Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89, 309 (1997) https://doi.org/10.1016/S0092-8674(00)80209-3
  7. Kondo, H. Guo, J. and Bringhurst, F. R. : Cyclic adenosine monophosphate/lprotein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteopro-tegerin mRNAs by marrow stromal cells. J. Bone Miner. Res. 17, 1667 (2002) https://doi.org/10.1359/jbmr.2002.17.9.1667
  8. Kaji, H., Sugimoto, T., Kanatani, M., Fukase, M., Kumegawa, M. and Chihara, K. : Prostaglandin $E_2$ stimulates osteoclast-like cell formation and bone-resorbing activity via osteoblasts: role of cAMP-dependent protein kinase. J. Bone Miner. Res. 11, 62 (1996)
  9. Fu, Q., Jilka, R. L., Manolagas, S. C. and O'Brien, C. A. : Parathyroid hormone stimulates receptor activator of NF-$\kappa$B ligand and inhibits osteoprotegerin expression via protein kinase A activation of cAMP-response element-binding pro-tein. J. Biol. Chem. 277, 48868 (2002) https://doi.org/10.1074/jbc.M208494200
  10. Antoni, F. A. : Molecular diversity of cyclic AMP signaling. Front Neuroendocrinol. 21, 103 (2000) https://doi.org/10.1006/frne.1999.0193
  11. Essayan, D. M. : Cyclic nucleotide phosphodiesterases. J Allergy Clin. Immunol. 108, 671 (2001) https://doi.org/10.1067/mai.2001.119555
  12. Kinoshita, T., Kobayashi, S., Ebara, S., Yoshimura, Y., Horiuchi, H., Tsutsumimoto, T., Wakabayashi, S. and Takaoka, K. : Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice. Bone 27, 811 (2000) https://doi.org/10.1016/S8756-3282(00)00395-1
  13. Waki, Y., Horita, T., Miyamoto, K., Ohya, K. and Kasugai, S. : Ettects of XT-44, a phosphodiesterase 4 inhibitor, in osteoblastgenesis and osteoclastgenesis in culture and itstherapeytic effects in rat ostepenia models. Jpn. J. Pharmacol. 79, 477 (1999) https://doi.org/10.1254/jjp.79.477
  14. Miyamoto, K., Waki, Y., Horita, T., Kasugai, S. and Ohya, K. : Reduction of bone loss by denbufylline, an inhibitor of phosphodiesterase 4. Biochem. Pharmacol. 54, 613 (1997) https://doi.org/10.1016/S0006-2952(97)00211-6
  15. Rawadi, G., Ferrer, C., SpinelIa-Jaegle, S., Roman-Roman, S., Bouali, Y. and Baron, R. : 1-(5-oxohexyI)-3,7-Dimethylxanthine, a phosphodiesterase inhibitor, activates MAPK cascades and promotes osteoblast differentiation by a mechanism independent of PKA activation. Endocrinology 142, 4673 (2001) https://doi.org/10.1210/en.142.11.4673
  16. Tam, C. S., Heersche, J. N., Murray, T. M. and Parsons, J. A. : Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology 110, 506 (1982) https://doi.org/10.1210/endo-110-2-506