DOI QR코드

DOI QR Code

Isopsoralen Induces Differentiation of Prechondrogenic ATDC5 Cells via Activation of MAP Kinases and BMP-2 Signaling Pathways

  • Li, Liang (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University) ;
  • Eun, Jae-Soon (College of Pharmacy, Woosuk University) ;
  • Nepal, Manoj (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University) ;
  • Ryu, Jae-Ha (College of Pharmacy, Research Center for Cell Fate Control, Sookmyung Women's University) ;
  • Cho, Hyoung-Kwon (Hanpoong Pharm & Foods Co. Ltd.) ;
  • Choi, Bo-Yun (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University) ;
  • Soh, Yun-Jo (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University)
  • 투고 : 2012.03.12
  • 심사 : 2012.05.03
  • 발행 : 2012.05.31

초록

Endochondral bone formation is the process by which mesenchymal cells condense to become chondrocytes, which ultimately form new bone. The process of chondrogenic differentiation and hypertrophy is critical for bone formation and as such is regulated by many factors. In this study, we aimed to indentify novel factors that regulate chondrogenesis. We investigated the possible role of isopsoralen in induction of chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Isopsoralen treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. Further, ATDC5 cells treated with isopsoralen were stained more intensely with Alcian blue than control cells, suggesting that isopsoralen increases the synthesis of matrix proteoglycans. Similarly, isopsoralen markedly induced the activation of alkaline phosphatase activity compared with control cells. Isopsoralen enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, OCN, Smad4 and Sox9 in a time-dependent manner. Furthermore, isopsoralen induced the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase, but not that of c-jun N-terminal kinase (JNK). Isopsoralen significantly enhanced the protein expression of BMP-2 in a time-dependent manner. PD98059 and SB 203580, inhibitors of ERK and p38 MAPK, respectively, decreased the number of stained cells treated with isopsoralen. Taken together, these results suggest that isopsoralen mediates a chondromodulating effect by BMP-2 or MAPK signaling pathways, and is therefore a possible therapeutic agent for bone growth disorders.

키워드

참고문헌

  1. Akiyama, H., Shukunami, C., Nakamura, T. and Hiraki, Y. (2000) Differential expressions of BMP family genes during chondrogenic differentiation of mouse ATDC5 cells. Cell Struct. Funct. 25, 195-204. https://doi.org/10.1247/csf.25.195
  2. Brighton, C. T. and Hunt, R. M. (1986) Histochemical localization of calcium in the fracture callus with potassium pyroantimonate. Possible role of chondrocyte mitochondrial calcium in callus calcification. J. Bone Joint Surg. Am. 68, 703-715.
  3. Brighton, C. T., Sugioka, Y. and Hunt, R. M. (1973) Cytoplasmic structures of epiphyseal plate chondrocytes. Quantitative evaluation using electron micrographs of rat costochondral junctions with special reference to the fate of hypertrophic cells. J. Bone Joint Surg. Am. 55, 771-784.
  4. Choi, H. J., Nepal, M., Park, Y. R., Lee, H. K., Oh, S. R. and Soh, Y. (2011) Stimulation of chondrogenesis in ATDC5 chondroprogenitor cells and hypertrophy in mouse by Genkwadaphnin. Eur. J. Pharmacol. 655, 9-15. https://doi.org/10.1016/j.ejphar.2011.01.012
  5. Davis, R. J. (2000) Signal transduction by the JNK group of MAP kinases. Cell 103, 239-252. https://doi.org/10.1016/S0092-8674(00)00116-1
  6. Enomoto, H., Furuichi, T., Zanma, A., Yamana, K., Yoshida, C., Sumitani, S., Yamamoto, H., Enomoto-Iwamoto, M., Iwamoto, M. and Komori, T. (2004) Runx2 defi ciency in chondrocytes causes adipogenic changes in vitro. J. Cell Sci. 117, 417-425.
  7. Furumatsu, T., Shukunami, C., Amemiya-Kudo, M., Shimano, H. and Ozaki, T. (2010) Scleraxis and E47 cooperatively regulate the Sox9-dependent transcription. Int. J. Biochem. Cell Biol. 42, 148-156. https://doi.org/10.1016/j.biocel.2009.10.003
  8. Ganan, Y., Macias, D., Duterque-Coquillaud, M., Ros, M. A. and Hurle, J. M. (1996) Role of TGF beta s and BMPs as signals controlling the position of the digits and the areas of interdigital cell death in the developing chick limb autopod. Development 122, 2349-2357.
  9. Grunder, T., Gaissmaier, C., Fritz, J., Stoop, R., Hortschansky, P., Mollenhauer, J. and Aicher, W. K. (2004) Bone morphogenetic protein (BMP)-2 enhances the expression of type II collagen and aggrecan in chondrocytes embedded in alginate beads. Osteoarthritis Cartilage 12, 559-567. https://doi.org/10.1016/j.joca.2004.04.001
  10. Guo, J., Wu, H., Weng, X., Yan, J. and Bi, K. (2003) Studies on extraction and isolation of active constituents from Psoralen corylifolia L. and the antitumor effect of the constituents in vitro. Zhong Yao Cai 26, 185-187.
  11. Hinoi, E., Takarada, T., Fujimori, S., Wang, L., Iemata, M., Uno, K. and Yoneda, Y. (2007) Nuclear factor E2 p45-related factor 2 negatively regulates chondrogenesis. Bone 40, 337-344. https://doi.org/10.1016/j.bone.2006.08.016
  12. Kong, L. D., Tan, R. X., Woo, A. Y. and Cheng, C. H. (2001) Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: implications for the treatment of affective disorders. Pharmacol. Toxicol. 88, 75-80. https://doi.org/10.1034/j.1600-0773.2001.088002075.x
  13. Kronenberg, H. M. (2003) Developmental regulation of the growth plate. Nature 423, 332-336. https://doi.org/10.1038/nature01657
  14. Lim, S. H., Ha, T. Y., Kim, S. R., Ahn, J., Park, H. J. and Kim, S. (2009) Ethanol extract of Psoralea corylifolia L. and its main constituent, bakuchiol, reduce bone loss in ovariectomised Sprague-Dawley rats. Br. J. Nutr. 101, 1031-1039. https://doi.org/10.1017/S0007114508066750
  15. Nakajima, S., Naruto, T., Miyamae, T., Imagawa, T., Mori, M., Nishimaki, S. and Yokota, S. (2009) Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells. Cytokine 47, 91-97. https://doi.org/10.1016/j.cyto.2009.05.002
  16. Nakamura, K., Shirai, T., Morishita, S., Uchida, S., Saeki-Miura, K. and Makishima, F. (1999) p38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth/differentiation factor-5 in ATDC5 cells. Exp. Cell Res. 250, 351-363. https://doi.org/10.1006/excr.1999.4535
  17. Netter Frank, H. (1988) Musculoskeletal system: anatomy, physiology, and metabolic disorders. W.B. Saunders Co, Philadelphia.
  18. Pae, H. O., Cho, H., Oh, G. S., Kim, N. Y., Song, E. K., Kim, Y. C., Yun, Y. G., Kang, C. L., Kim, J. D., Kim, J. M. and Chung, H. T. (2001) Bakuchiol from Psoralea corylifolia inhibits the expression of inducible nitric oxide synthase gene via the inactivation of nuclear transcription factor-kappaB in RAW 264.7 macrophages. Int. Immunopharmacol. 1, 1849-1855. https://doi.org/10.1016/S1567-5769(01)00110-2
  19. Park, C. K., Lee, Y., Chang, E. J., Lee, M. H., Yoon, J. H., Ryu, J. H. and Kim, H. H. (2008) Bavachalcone inhibits osteoclast differentiation through suppression of NFATc1 induction by RANKL. Biochem. Pharmacol. 75, 2175-2182. https://doi.org/10.1016/j.bcp.2008.03.007
  20. Rockel, J. S., Bernier, S. M. and Leask, A. (2009) Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFalpha- induced MEK/ERK signalling. Arthritis Res. Ther. 11, R8. https://doi.org/10.1186/ar2595
  21. Shukunami, C., Ishizeki, K., Atsumi, T., Ohta, Y., Suzuki, F. and Hiraki, Y. (1997) Cellular hypertrophy and calcifi cation of embryonal carcinoma-derived chondrogenic cell line ATDC5 in vitro. J. Bone Miner. Res. 12, 1174-1188. https://doi.org/10.1359/jbmr.1997.12.8.1174
  22. Shukunami, C., Ohta, Y., Sakuda, M. and Hiraki, Y. (1998) Sequential progression of the differentiation program by bone morphogenetic protein-2 in chondrogenic cell line ATDC5. Exp. Cell Res. 241, 1-11. https://doi.org/10.1006/excr.1998.4045
  23. Shukunami, C., Shigeno, C., Atsumi, T., Ishizeki, K., Suzuki, F. and Hiraki, Y. (1996) Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor. J. Cell Biol. 133, 457-468. https://doi.org/10.1083/jcb.133.2.457
  24. Stanton, L. A., Underhill, T. M. and Beier, F. (2003) MAP kinases in chondrocyte differentiation. Dev. Biol. 263, 165-175. https://doi.org/10.1016/S0012-1606(03)00321-X
  25. Sultan, T. and Ali, S. A. (2011) Psoralea corylifolia extracts stimulate cholinergic-like psoralen receptors of tadpole-tail melanophores, leading to skin darkening. J. Recept. Signal. Transduct. Res. 31, 39-44. https://doi.org/10.3109/10799893.2010.508164
  26. Sun, N. J., Woo, S. H., Cassady, J. M. and Snapka, R. M. (1998) DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia. J. Nat. Prod. 61, 362-366. https://doi.org/10.1021/np970488q
  27. Tang, D. Z., Yang, F., Yang, Z., Huang, J., Shi, Q., Chen, D. and Wang, Y. J. (2011) Psoralen stimulates osteoblast differentiation through activation of BMP signaling. Biochem. Biophys. Res. Commun. 405, 256-261. https://doi.org/10.1016/j.bbrc.2011.01.021
  28. Wahl, M. B., Heinzmann, U. and Imai, K. (2005) LongSAGE analysis revealed the presence of a large number of novel antisense genes in the mouse genome. Bioinformatics 21, 1389-1392. https://doi.org/10.1093/bioinformatics/bti205
  29. Wang, D., Li, F. and Jiang, Z. (2001) Osteoblastic proliferation stimulating activity of Psoralea corylifolia extracts and two of its flavonoids. Planta Med. 67, 748-749. https://doi.org/10.1055/s-2001-18343
  30. Zhang, C. Z., Wang, S. X., Zhang, Y., Chen, J. P. and Liang, X. M. (2005) In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J. Ethnopharmacol. 98, 295-300. https://doi.org/10.1016/j.jep.2005.01.033

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