Inhibition of ALK5 signaling induces physeal dysplasia in rats

Toxicologic Pathology

Volumn 35, Issue 2, 2007, Pages 284-295

  Frazier, Kendall ^a   Thomas, Roberta ^a   Scicchitano, Marshall ^a   Mirabile, Rosanna ^a   Boyce, Rogely ^a   Zimmerman, Dawn ^a   Grygielko, Eugene ^a   Nold, James ^a   DeGouville, Anne Charlotte ^a   Huet, Stephane ^a   Laping, Nicholas ^a   Gellibert, Francoise ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Mechanisms of toxicity; Microdissection; Molecular pathology; Musculoskeletal system; Preclinical safety assessment risk management; Rat pathology

Indexed keywords

ACTIVIN LIKE KINASE 5 RECEPTOR; BASIC FIBROBLAST GROWTH FACTOR; GW 788388; OSTEOGENIC PROTEIN 1; PARATHYROID HORMONE RELATED PROTEIN; PYRAZOLE DERIVATIVE; RECEPTOR SUBTYPE; SOMATOMEDIN C; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BONE DYSPLASIA; BONE MATRIX; BONE STRUCTURE; CARTILAGE CELL; CELL HYPERPLASIA; CELL PROLIFERATION; CONTROLLED STUDY; FEMUR; GENETIC TRANSCRIPTION; HISTOPATHOLOGY; HYPEROSTOSIS; HYPERTROPHY; IMMUNOHISTOCHEMISTRY; LASER MICRODISSECTION; NICK END LABELING; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TOXICITY TESTING; ZYMOGRAPHY;

ACTIVIN RECEPTORS, TYPE I; ANIMALS; BENZAMIDES; BONE DISEASES, DEVELOPMENTAL; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION; GROWTH PLATE; PYRAZOLES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

RATTUS;

EID: 33847775958     PISSN: 01926233     EISSN: 15331601     Source Type: Journal    
DOI: 10.1080/01926230701198469     Document Type: Article

References (51)

1. Alvarez, J., Horton, J., Sohn, P., and Serra, R. (2001). The perichondrium plays an important role in mediating the effects of TGF-β1 on endochondral bone formation. Devel Dynam 221, 311-21.
2. Alvarez, J., Sohn, P., Zeng, X., Doetschman, T., Robbins, D. J., and Serra, R. (2002). TGF-β2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development 129, 1913-24.
3. Amizuka, N., Warshawsky, H., Henderson, J. E., White, J. H., Karaplis, A. C., Goltzman, D., Sasaki, T., and Ozawa, H. (1994). Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. J Cell Biol 126, 1611-23.
4. Baron, J., Klein, K. O., Yanovski, J. A., Novosad, J. A., Bacher, J. D., Bolander, M. E., and Cutler, Jr. G. B. (1994) Induction of growth plate cartilage ossification by basic fibroblast growth factor. Endocrinol 135, 2790-3.
5. Borden, P., Solymar, D., Sucharczuk, A., Lindman, B., Cannon, P., and Heller, R. A. (1996). Cytokine control of interstitial collagenase and collagenase-3 gene expression in human chondrocytes. J Biol Chem 271, 23577-81.
6. Border, W. A., and Noble, N. A. (1994). Transforming growth factor beta in tissue fibrosis. N Engl J Med 10, 1286-92.
7. Brown, A. P., Courtney, C. L., King, L. M., Groom, S. C., and Graziano, M. J. (2005). Cartilage dysplasia and tissue mineralization in the rat following administration of a FGF receptor tyrosine kinase inhibitor. Toxicol Pathol 33, 449-55.
8. Callahan, J. F., Burgess, J. L., Fornwald, J. A., Gaster, L. M., Harling, J. D., Harrington, F. P., Heer, J., Kwon, C., Lehr, R., Mathur, A., Olson, B. A., Weinstock, J., and Laping, N. J. (2002) Identification of novel inhibitors of the transforming growth factor-beta type 1 receptor (ALK5). J Med Chem 45, 999-1001.
9. Cetin, E., Girsch, W., Brand, G., Thurnher, D., Cetin, E. M., and Trieb, K. (2004). Distinct Expression of APO-1/FAS and caspase-8 in the human growth plate. Calcified Tissue Int 74, 181-6.
10. Chrysis, D., Nilsson, O., Ritzen, E. M., and Savendahl, L. (2002). Apoptosis is developmentally regulated in rat growth plate. Endocrine 18, 271-8.
11. Cross, M. J., and Claesson-Welsh, L. (2001). FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 22, 201-7.
12. Dalmas, D. A., Scicchitano, M. S., Zimmerman, D., Tierney, L. A., and Boyce, R. W. (2005). Target gene localization using laser-capture microdissection and real-time reverse transcription-polymerase chain reaction analysis. J Histotechnol 28, 177-80.
13. Datto, M. B., Frederick, J. P., Pan, L., Borton, A. J., Zhuang, Y., and Wang, X. F. (1999). Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. Mol Cell Biol 19, 2495-504.
14. Ferguson, C. M., Schwarz, E. M., Reynolds, P. R., Puzas, J. E., Rosier, R. N., and O'Keefe, R. J. (2000). Smad2 and 3 mediate transforming growth factor-β1-induced inhibition of chondrocyte maturation. Endocrinol 141, 4728-35.
15. Fredericks, W., and Mook, O. (2004). Metabolic mapping of proteinase activity with emphasis on in situ zymography of gelatinases: review and protocols. J Histochem Cytochem 54, 711-22.
16. Gellibert F., de Gouville A. C., Woolven J., Mathews N., Nguyen V. L., Bertho-Ruault C., Patikis A., Grygielko E. T., Laping N. J., and Huet S. (2006). Discovery of 4-4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl-N-(tetrahydro- 2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor. J Med Chem 49(7), 2210-21.
17. Gerber, H. P., Vu, T. H., Ryan, A. M., Kowalski, J., Werb, Z., and Ferrara, N. (1999). VEGF couples hypertrophic cartilage remodelling, ossification and angiogenesis during endochondral bone formation. Nat Med 5, 623-8.
18. Grimsrud, C. D., Rosier, R. N., Puzas, J. E., Reynolds, P. R., Reynolds, S. D., Hicks, D. G., and O'Keefe, R. J. (1998). Bone morphogenetic protein-7 in growth-plate chondrocytes: regulation by retinoic acid is dependent on the stage of chrondrocyte maturation. J Orthop Res 16, 247-55.
19. Grygielko, E. T., Martin, W. M., Tweed, C., Thornton, P., Harling, J., Brooks, D. P., and Laping, N. J. (2005). Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Therapeut 313, 943-51.
20. Hoivik, D. J., Qualls, C. W. Jr., Mirabile, R. C., Cariello, N. F., Kimbrough, C. L., Colton, H. M., Anderson, S. P., Santostefano, M. J., Morgan, R. J., Dahl, R. R., Brown, A. R., Zhao, Z., Mudd, P. N. Jr., Oliver, W. B. Jr., Brown, H. R., and Miller, R. T. (2004). Fibrates induce hepatic peroxisome and mitochondrial proliferation without overt evidence of cellular proliferation and oxidative stress in cynomolgus monkeys. Carcinogenesis 25, 1757-69.
21. Inman, G. J., Nicolas, F. J., Callahan, J. F., Harling, J. D., Gaster, L. M., Reith, A. D., Laping, N. J., and Hill, C. S. (2002) SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Molec Pharmacol 62(1), 65-74.
22. Jacquet, R., Hillyer, J., and Landis, W. J. (2005). Laser capture microdissection and reverse-transcriptase polymerase chain reaction of connective tissues. Analyt Biochem 337, 22-34.
23. Karaplis, A. C., Luz, A., Glowacki, J., Bronson, R. T., Tybulewicz, V. L., Kronenberg, H. M., and Mulligan, R. C. (1994).Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev 8, 277-89.
24. Landis, W. J., Jacquet, R., Hillyer, J., and Zhang, J. (2003). Analysis of osteopontin in mouse growth plate cartilage by application of laser capture microdissection and RT-PCR. Connective Tissue Res 44(Suppl. 1), 28-32.
25. Laping, N. J. (2003). ALK5 inhibition in renal disease. Curr Opin Pharmacol 3, 204-8.
26. Laping, N. J., Grygielko, E., Mathur, A., Butter, S., Bomberger, J., Tweed, C., Martin, W., Fornwald, J., Lehr, R., Harling, J., Gaster, L., Callahan, J. F., and Olson, B. A. (2002). Inhibition of transforming growth factor (TGF)-β1-induced extracellular matrix with a novel inhibitor of the TGF-β type 1 receptor kinase activity: SB-431542. Molec Pharmacol 62, 58-64.
27. Lee, E. R., Murphy, G., El-Alfy, M., Davoli, M. A., Lamplugh, L., Docherty, A. J., and Leblond, C. P. (1999). Active gelatinase B is identified by histozymography in the cartilage resorption sites of developing long bones. Dev Dyn 215, 190-215.
28. Liu, Z., Xu, J., Colvin, J. S., and Ornitz, D. M. (2002). Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev 16(7), 859-69.
29. Loveys, L. S., Gelb, D., Hurwitz, S. R., Puzas, J. E., and Rosier, R. N. (1993). Effects of parathyroid hormone-related peptide on chick growth plate chondrocytes. J Orthop Res 11, 884-91.
30. Matsunaga, S., Yamamoto, T., and Fukumura, K. (1999). Temporal and spatial expressions of transforming growth factor-betas and their receptors in epiphyseal growth plate. Int J Oncol 14, 1063-7.
31. Mook, O., Overbeek, C., Ackema, E., Maldegem, F., and Frederiks, W. (2003) In situ localization of gelatinolytic activity in the extracellular matrix of metastases of colon cancer in rat liver using quenched fluorogenic dg-gelatin. J Histochem Cytochem 51(6), 821-29.
32. Nakamura, T., Miller, D., Ruoslahti, E., and Border, W. A. (1992). Production of extracellular matrix by glomerular epithelial cells is regulated by transforming growth factor-beta 1. Kidney Int 41, 1213-21.
33. Nazatsky, E., Azran, E., Dean, D. D., Boyan, B. D., and Schwartz, Z. (2000). Parathyroid hormone and transforming growth factor-beta1 coregulate chondrocyte differentiation in vitro. Endocrine 13, 305-12.
34. Olzinski, A. R., McCafferty, T. A., Zhao, S. Q., Behm, D. J., Eybye, M. E., Maniscalco, K., Frazier, K. S., Mirabile, R., Douglas, S. A., Coatney, R.W., and Willette, R. N. (2005). Hypertensive target organ damage is attenuated by a p38 mapk inhibitor: role of systemic blood pressure and endothelial protection. Cardiovascular Res 66, 170-8.
35. Ortega, N., Behonick, D., Stickens, D., and Werb, Z. (2003). How proteases regulate bone morphogenesis. Ann N Y Acad Sci 995, 109-16.
36. Pateder, D. B., Rosier, R. N., Schwarz, E. M., Reynolds, P. R., Puzas, J. E., D'Souza, M., and O'Keefe, R. J. (2000). PTHrP expression in chondrocytes, regulation by TGF-β, and interactions between epiphyseal and growth plate chondrocytes. Exper Cell Res 256, 555-62.
37. Pavasant, P., Shizari, T., and Underhill, C. B. (1996). Hyaluronan synthesis by epiphyseal chondrocytes is regulated by growth hormone, insulin-like growth factor-1, parathyroid hormone and transforming growth factor-beta 1. Matrix Biol 15, 423-32.
38. Ryan, A. M., Eppler, D. B., Hagler, K. E., Bruner, R. H., Thomford, P. J., Hall, R. L., Shopp, G. M., and O'Neill, C. A. (1999). Preclinical safety evaluation of rhuMabVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol Pathol 27, 78-86.
39. Serra, R., Johnson, M., Filvaroff, E. H., LaBorde, J., Sheehan, D. M., Derynck, R., and Moses, H. L. (1997). Expression of a truncated, kinase-defective TGF-β type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J Cell Biol 139, 541-52.
40. Serra, R., Karapalis, A., and Sohn, P. (1999). PTHrP-dependent and independent effects on TGF-β on endochondral bone formation. J Cell Biol 145, 783-94.
41. Stickens, D., Behonick, D. J., Ortega, N., Heyer, B., Hartenstein, B., Yu, Y., Fosang, A. J., Schorpp-Kistner, M., Angel, P., and Werb, Z. (2004). Altered endochdondral bone development in matrix metalloproteinase 13-deficient mice. Development 131, 5883-95.
42. Tchetina, E., Mwale, F., and Poole, A. R. (2003). Distinct phases of coordinated early and late gene expression in growth plate chondrocytes in relationship to cell proliferation, matrix assembly, remodelling, and cell differentiation. J Bone Mineral Res 18, 844-51.
43. Terkeltaub, R. A., Johnson, K., Rohnow, D., Goomer, R., Burton, D., and Deftos, L. J. (1998). Bone morphogenetic proteins and bFGF exert opposing regulatory effects on PTHrP expression and inorganic pyrophosphate elaboration in immortalized murine endochondral hypertrophic chondrocytes (MCT cells). J Bone Mineral Res 13, 931-41.
44. Uria, J. A., Balbin, M., Lopez, J. M., Alvarez, J., Vizoso, F., Takigawa, M., and Lopez-Otin, C. (1998a). Collagenase-3 (MMP-13) expression in chondrosarcoma cells and its regulation by basic fibroblast growth factor. Am J Pathol 153, 91-101.
45. Uria, J. A., Jimenez, M. J., Balbin, M., Freije, J. M., and Lopez-Otin, C. (1998b). Differential effects of TGF-β on the expression of collagenase-1 and collagenase-3 in human fibroblasts. J Biol Chem 273, 9769-77.
46. Van Der Eerden, B. C. J., Karperien, M., and Wit, J. M. (2003). Systemic and local regulation of the growth plate. Endocr Rev 24, 782-801.
47. Vu, T. H., Shipley, J. M., Bergers, G., Berger, J. E., Helms, J. A., Hanahan, D., Shapiro, S. D., Senior, R. M., and Werb, Z. (1998). MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93, 411-22.
48. Wang, J., Zhou, J., and Bondy, C. A. (1999). Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. FASEB J 13, 1985-90.
49. Wedge, S. R., Ogilvie, D. J., Dukes, M., Kendrew, J., Curwen, J. O., Hennequin, L. F., Thomas, A. P., Stokes, E. S., Curry, B., Richmond, G. H., and Wadsworth, P. F. (2000). ZD4190: an orally active inhibitor of vascular endothelial growth factor signaling with broad-spectrum antitumor efficacy. Cancer Res 60, 970-5.
50. Wu, W., Tchetina, E., Mwale, F., Hasty, K., Pidoux, I., Reiner, A., Chen, J., Van Wart, H. E., and Poole, A. R. (2002). Proteolysis involving MMP-13 (collagenase-3) and the expression of the chondrocyte hypertrophic phenotype. J Bone Miner Res 17, 639-51.
51. Yang, X., Chen, L., Xu, X., Li, C., Huang, C., and Deng, C. X. (2001). TGF-β/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol 153, 35-46.