The Ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation

Human Molecular Genetics

Volumn 22, Issue 15, 2013, Pages

  Ono, Koichiro ^a,c   Karolak, Matthew R ^b   de la Croix Ndong, Jean ^a   Wang, Weixi ^a   Yang, Xiangli ^a   Elefteriou, Florent ^a  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Spinal Surgery Section Kawasaki   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 9; COLLAGEN TYPE 2; COLLAGENASE 3; FIBROBLAST GROWTH FACTOR RECEPTOR; GELATINASE B; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NEUROFIBROMIN; RAS PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CARTILAGE CELL; CELL CULTURE; CELL MATURATION; CELL PROLIFERATION; DWARFISM; ENCHONDRAL OSSIFICATION; ENZYME ACTIVITY; ENZYME INHIBITION; GAIN OF FUNCTION MUTATION; GENOTYPE; IN VITRO STUDY; MITOSIS; MOUSE; NONHUMAN; OSTEOCLASTOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ANIMAL; BONE DEVELOPMENT; CHONDROGENESIS; GENE EXPRESSION; GENETICS; GROWTH PLATE; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY;

ANIMALS; APOPTOSIS; CELL PROLIFERATION; CHONDROCYTES; CHONDROGENESIS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GENE EXPRESSION; GROWTH PLATE; MICE, KNOCKOUT; NEUROFIBROMIN 1; OSTEOGENESIS; RECEPTORS, FIBROBLAST GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84880289335     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddt162     Document Type: Article

References (105)

1. Kronenberg, H.M. (2003) Developmental regulation of the growth plate. Nature, 423, 332-336.
2. Farnum, C.E., Lee, R., O'Hara, K. and Urban, J.P. (2002) Volume increase in growth plate chondrocytes during hypertrophy: the contribution of organic osmolytes. Bone, 30, 574-581.
3. St-Jacques, B., Hammerschmidt, M. and McMahon, A.P. (1999) Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev., 13, 2072-2086.
4. Maeda, Y., Nakamura, E., Nguyen, M.T., Suva, L.J., Swain, F.L., Razzaque, M.S., Mackem, S. and Lanske, B. (2007) Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone. Proc. Natl Acad. Sci. USA, 104, 6382-6387.
5. Long, F., Zhang, X.M., Karp, S., Yang, Y. and McMahon, A.P. (2001) Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development, 128, 5099-5108.
6. Chung, U.I., Schipani, E., McMahon, A.P. and Kronenberg, H.M. (2001) Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development. J. Clin. Invest., 107, 295-304.
7. Vortkamp, A., Lee, K., Lanske, B., Segre, G.V., Kronenberg, H.M. and Tabin, C.J. (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science, 273, 613-622.
8. Shao, Y.Y., Wang, L. and Ballock, R.T. (2006) Thyroid hormone and the growth plate. Rev. Endocr. Metab. Disord., 7, 265-271.
9. Lian, J.B., McKee, M.D., Todd, A.M. and Gerstenfeld, L.C. (1993) Induction of bone-related proteins, osteocalcin and osteopontin, and their matrix ultrastructural localization with development of chondrocyte hypertrophy in vitro. J. Cell. Biochem., 52, 206-219.
10. Shanahan, C.M., Cary, N.R., Metcalfe, J.C. and Weissberg, P.L. (1994) High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J. Clin. Invest., 93, 2393-2402.
11. Addison, W.N., Azari, F., Sorensen, E.S., Kaartinen, M.T. and McKee, M.D. (2007) Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, up-regulating osteopontin, and inhibiting alkaline phosphatase activity. J. Biol. Chem., 282, 15872-15883.
12. Sodek, J., Ganss, B. and McKee, M.D. (2000) Osteopontin. Crit. Rev. Oral Biol. Med., 11, 279-303.
13. 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, 411-422.
14. Gerber, H.P., Vu, T.H., Ryan, A.M., Kowalski, J., Werb, Z. and Ferrara, N. (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat. Med., 5, 623-628.
15. Xiong, J., Onal, M., Jilka, R.L., Weinstein, R.S., Manolagas, S.C. and O'Brien, C.A. (2011) Matrix-embedded cells control osteoclast formation. Nat. Med., 17, 1235-1241.
16. Krejci, P., Masri, B., Fontaine, V., Mekikian, P.B., Weis, M., Prats, H. and Wilcox, W.R. (2005) Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis. J. Cell Sci., 118, 5089-5100.
17. Inada, M., Wang, Y., Byrne, M.H., Rahman, M.U., Miyaura, C., Lopez-Otin, C. and Krane, S.M. (2004) Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. Proc. Natl Acad. Sci. USA, 101, 17192-17197.
18. Mackie, E.J., Tatarczuch, L. and Mirams, M. (2011) The skeleton: a multi-functional complex organ: the growth plate chondrocyte and endochondral ossification. J. Endocrinol., 211, 109-121.
19. Muenke, M., Schell, U., Hehr, A., Robin, N.H., Losken, H.W., Schinzel, A., Pulleyn, L.J., Rutland, P., Reardon, W., Malcolm, S. et al. (1994) A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat. Genet., 8, 269-274.
20. Oldridge, M., Wilkie, A.O., Slaney, S.F., Poole, M.D., Pulleyn, L.J., Rutland, P., Hockley, A.D., Wake, M.J., Goldin, J.H., Winter, R.M. et al. (1995) Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome. Hum. Mol. Genet., 4, 1077-1082.
21. Wilkie, A.O., Slaney, S.F., Oldridge, M., Poole, M.D., Ashworth, G.J., Hockley, A.D., Hayward, R.D., David, D.J., Pulleyn, L.J., Rutland, P. et al. (1995) Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat. Genet., 9, 165-172.
22. Shiang, R., Thompson, L.M., Zhu, Y.Z., Church, D.M., Fielder, T.J., Bocian, M., Winokur, S.T. and Wasmuth, J.J. (1994) Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell, 78, 335-342.
23. Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.M., Maroteaux, P., Le Merrer, M. and Munnich, A. (1994) Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature, 371, 252-254.
24. Bellus, G.A., Hefferon, T.W., Ortiz de Luna, R.I., Hecht, J.T., Horton, W.A., Machado, M., Kaitila, I., McIntosh, I. and Francomano, C.A. (1995) Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am. J. Hum. Genet., 56, 368-373.
25. White, K.E., Cabral, J.M., Davis, S.I., Fishburn, T., Evans, W.E., Ichikawa, S., Fields, J., Yu, X., Shaw, N.J., McLellan, N.J. et al. (2005) Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am. J. Hum. Genet., 76, 361-367.
26. Yoon, B.S., Pogue, R., Ovchinnikov, D.A., Yoshii, I., Mishina, Y., Behringer, R.R. and Lyons, K.M. (2006) BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways. Development, 133, 4667-4678.
27. Lax, I., Wong, A., Lamothe, B., Lee, A., Frost, A., Hawes, J. and Schlessinger, J. (2002) The docking protein FRS2alpha controls a MAP kinase-mediated negative feedback mechanism for signaling by FGF receptors. Mol. Cell, 10, 709-719.
28. Wong, A., Lamothe, B., Lee, A., Schlessinger, J. and Lax, I. (2002) FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl. Proc. Natl Acad. Sci. USA, 99, 6684-6689.
29. Mason, J.M., Morrison, D.J., Bassit, B., Dimri, M., Band, H., Licht, J.D. and Gross, I. (2004) Tyrosine phosphorylation of Sprouty proteins regulates their ability to inhibit growth factor signaling: a dual feedback loop. Mol. Biol. Cell, 15, 2176-2188.
30. Eswarakumar, V.P., Lax, I. and Schlessinger, J. (2005) Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev., 16, 139-149.
31. Murakami, S., Balmes, G., McKinney, S., Zhang, Z., Givol, D. and de Crombrugghe, B. (2004) Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype. Genes Dev., 18, 290-305.
32. Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M. et al. (2004) Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Nat. Med., 10, 80-86.
33. Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D.J., Bell, S.M., Bullens, S., Bunting, S. et al. (2012) Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. Am. J. Hum. Genet., 91, 1108-1114.
34. Bundschu, K., Knobeloch, K.P., Ullrich, M., Schinke, T., Amling, M., Engelhardt, C.M., Renne, T., Walter, U. and Schuh, K. (2005) Gene disruption of Spred-2 causes dwarfism. J. Biol. Chem., 280, 28572-28580.
35. Martin, G.A., Viskochil, D., Bollag, G., McCabe, P.C., Crosier, W.J., Haubruck, H., Conroy, L., Clark, R., O'Connell, P., Cawthon, R.M. et al. (1990) The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell, 63, 843-849.
36. Basu, T.N., Gutmann, D.H., Fletcher, J.A., Glover, T.W., Collins, F.S. and Downward, J. (1992) Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature, 356, 713-715.
37. Wang, W., Nyman, J.S., Ono, K., Stevenson, D.A., Yang, X. and Elefteriou, F. (2011) Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I. Hum. Mol. Genet., 20, 3910-3924.
38. Zhou, Y.X., Xu, X., Chen, L., Li, C., Brodie, S.G. and Deng, C.X. (2000) A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures. Hum. Mol. Genet., 9, 2001-2008.
39. Naski, M.C., Wang, Q., Xu, J. and Ornitz, D.M. (1996) Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia. Nat. Genet., 13, 233-237.
40. Li, C., Chen, L., Iwata, T., Kitagawa, M., Fu, X.Y. and Deng, C.X. (1999) A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors. Hum. Mol. Genet., 8, 35-44.
41. Wang, Y., Spatz, M.K., Kannan, K., Hayk, H., Avivi, A., Gorivodsky, M., Pines, M., Yayon, A., Lonai, P. and Givol, D. (1999) A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3. Proc. Natl Acad. Sci. USA, 96, 4455-4460.
42. Iwata, T., Chen, L., Li, C., Ovchinnikov, D.A., Behringer, R.R., Francomano, C.A. and Deng, C.X. (2000) A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos. Hum. Mol. Genet., 9, 1603-1613.
43. Segev, O., Chumakov, I., Nevo, Z., Givol, D., Madar-Shapiro, L., Sheinin, Y., Weinreb, M. and Yayon, A. (2000) Restrained chondrocyte proliferation and maturation with abnormal growth plate vascularization and ossification in human FGFR-3(G380R) transgenic mice. Hum. Mol. Genet., 9, 249-258.
44. Chen, L., Li, C., Qiao, W., Xu, X. and Deng, C. (2001) A Ser(365)->.Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia. Hum. Mol. Genet., 10, 457-465.
45. Delezoide, A.L., Benoist-Lasselin, C., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Vekemans, M. and Bonaventure, J. (1998) Spatio-temporal expression of FGFR 1, 2 and 3 genes during human embryo-fetal ossification. Mech. Dev., 77, 19-30.
46. Peters, K.G., Werner, S., Chen, G. and Williams, L.T. (1992) Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. Development, 114, 233-243.
47. Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A. and Leder, P. (1996) Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell, 84, 911-921.
48. Peters, K., Ornitz, D., Werner, S. and Williams, L. (1993) Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. Dev. Biol., 155, 423-430.
49. Ahrens, P.B., Solursh, M. and Reiter, R.S. (1977) Stage-related capacity for limb chondrogenesis in cell culture. Dev. Biol., 60, 69-82.
50. Du, X., Weng, T., Sun, Q., Su, N., Chen, Z., Qi, H., Jin, M., Yin, L., He, Q. and Chen, L. (2010) Dynamic morphological changes in the skulls of mice mimicking human Apert syndrome resulting from gain-of-function mutation of FGFR2 (P253R). J. Anat., 217, 97-105.
51. Lu, X., Su, N., Yang, J., Huang, W., Li, C., Zhao, L., He, Q., Du, X., Shen, Y., Chen, B. et al. (2009) Fibroblast growth factor receptor 1 regulates the differentiation and activation of osteoclasts through Erk1/2 pathway. Biochem. Biophys. Res. Commun., 390, 494-499.
52. Mangues, R., Corral, T., Lu, S., Symmans, W.F., Liu, L. and Pellicer, A. (1998) NF1 inactivation cooperates with N-ras in in vivo lymphogenesis activating Erk by a mechanism independent of its Ras-GTPase accelerating activity. Oncogene, 17, 1705-1716.
53. Lau, N., Feldkamp, M.M., Roncari, L., Loehr, A.H., Shannon, P., Gutmann, D.H. and Guha, A. (2000) Loss of neurofibromin is associated with activation of RAS/MAPK and PI3-K/AKT signaling in a neurofibromatosis 1 astrocytoma. J. Neuropathol. Exp. Neurol., 59, 759-767.
54. Harrisingh, M.C. and Lloyd, A.C. (2004) Ras/Raf/ERK signalling and NF1. Cell Cycle, 3, 1255-1258.
55. Zhu, Y., Romero, M.I., Ghosh, P., Ye, Z., Charnay, P., Rushing, E.J., Marth, J.D. and Parada, L.F. (2001) Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev., 15, 859-876.
56. Jacob, A.L., Smith, C., Partanen, J. and Ornitz, D.M. (2006) Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Dev. Biol., 296, 315-328.
57. Kuorilehto, T., Nissinen, M., Koivunen, J., Benson, M.D. and Peltonen, J. (2004) NF1 tumor suppressor protein and mRNA in skeletal tissues of developing and adult normal mouse and NF1-deficient embryos. J. Bone Miner. Res., 19, 983-989.
58. Chen, L., Adar, R., Yang, X., Monsonego, E.O., Li, C., Hauschka, P.V., Yayon, A. and Deng, C.X. (1999) Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. J. Clin. Invest., 104, 1517-1525.
59. Wang, Q., Green, R.P., Zhao, G. and Ornitz, D.M. (2001) Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains. Development, 128, 3867-3876.
60. Ornitz, D.M. (2005) FGF signaling in the developing endochondral skeleton. Cytokine Growth Factor Rev., 16, 205-213.
61. Naski, M.C., Colvin, J.S., Coffin, J.D. and Ornitz, D.M. (1998) Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development, 125, 4977-4988.
62. Sabbagh, Y., Carpenter, T.O. and Demay, M.B. (2005) Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc. Natl Acad. Sci. USA, 102, 9637-9642.
63. Miedlich, S.U., Zalutskaya, A., Zhu, E.D. and Demay, M.B. (2010) Phosphate-induced apoptosis of hypertrophic chondrocytes is associated with a decrease in mitochondrial membrane potential and is dependent upon Erk1/2 phosphorylation. J. Biol. Chem., 285, 18270-18275.
64. Ballock, R.T. and Reddi, A.H. (1994) Thyroxine is the serum factor that regulates morphogenesis of columnar cartilage from isolated chondrocytes in chemically defined medium. J. Cell Biol., 126, 1311-1318.
65. 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, 859-869.
66. Weizmann, S., Tong, A., Reich, A., Genina, O., Yayon, A. and Monsonego-Ornan, E. (2005) FGF upregulates osteopontin in epiphyseal growth plate chondrocytes: implications for endochondral ossification. Matrix Biol., 24, 520-529.
67. Mugniery, E., Dacquin, R., Marty, C., Benoist-Lasselin, C., de Vernejoul, M.C., Jurdic, P., Munnich, A., Geoffroy, V. and Legeai-Mallet, L. (2012) An activating Fgfr3 mutation affects trabecular bone formation via a paracrine mechanism during growth. Hum. Mol. Genet., 21, 2503-2513.
68. Legeai-Mallet, L., Benoist-Lasselin, C., Delezoide, A.L., Munnich, A. and Bonaventure, J. (1998) Fibroblast growth factor receptor 3 mutations promote apoptosis but do not alter chondrocyte proliferation in thanatophoric dysplasia. J. Biol. Chem., 273, 13007-13014.
69. 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 endochondral bone development in matrix metalloproteinase 13-deficient mice. Development, 131, 5883-5895.
70. Nishida, T., Kubota, S., Aoyama, E., Janune, D., Maeda, A. and Takigawa, M. (2011) Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes. Endocrinology, 152, 4232-4241.
71. Deckers, M.M., Van Beek, E.R., Van Der Pluijm, G., Wetterwald, A., Van DerWee-Pals, L.,Cecchini, M.G., Papapoulos, S.E. andLowik, C.W. (2002) Dissociation of angiogenesis and osteoclastogenesis during endochondral bone formation in neonatal mice. J. Bone Miner. Res., 17, 998-1007.
72. Nakashima, T., Hayashi, M., Fukunaga, T., Kurata, K., Oh-Hora, M., Feng, J.Q., Bonewald, L.F., Kodama, T., Wutz, A., Wagner, E.F. et al. (2011) Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat. Med., 17, 1231-1234.
73. Elefteriou, F., Benson, M.D., Sowa, H., Starbuck, M., Liu, X., Ron, D., Parada, L.F. and Karsenty, G. (2006) ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab., 4, 441-451.
74. Matsushita, T., Chan, Y.Y., Kawanami, A., Balmes, G., Landreth, G.E. and Murakami, S. (2009) Extracellular signal-regulated kinase 1 (ERK1) and ERK2 play essential roles in osteoblast differentiation and in supporting osteoclastogenesis. Mol. Cell. Biol., 29, 5843-5857.
75. Ek-Rylander, B., Flores, M., Wendel, M., Heinegard, D. and Andersson, G. (1994) Dephosphorylation of osteopontin and bone sialoprotein by osteoclastic tartrate-resistant acid phosphatase. Modulation of osteoclast adhesion in vitro. J. Biol. Chem., 269, 14853-14856.
76. Razzouk, S., Brunn, J.C., Qin, C., Tye, C.E., Goldberg, H.A. and Butler, W.T. (2002) Osteopontin posttranslational modifications, possibly phosphorylation, are required for in vitro bone resorption but not osteoclast adhesion. Bone, 30, 40-47.
77. Chrisman, T.D. and Garbers, D.L. (1999) Reciprocal antagonism coordinates C-type natriuretic peptide and mitogen-signaling pathways in fibroblasts. J. Biol. Chem., 274, 4293-4299.
78. Yamashita, Y., Takeshige, K., Inoue, A., Hirose, S., Takamori, A. and Hagiwara, H. (2000) Concentration of mRNA for the natriuretic peptide receptor-C in hypertrophic chondrocytes of the fetal mouse tibia. J. Biochem. (Tokyo). 127, 177-179.
79. Chusho, H., Tamura, N., Ogawa, Y., Yasoda, A., Suda, M., Miyazawa, T., Nakamura, K., Nakao, K., Kurihara, T., Komatsu, Y. et al. (2001) Dwarfism and early death in mice lacking C-type natriuretic peptide. Proc. Natl Acad. Sci. USA, 98, 4016-4021.
80. L'Hote, C.G. and Knowles, M.A. (2005) Cell responses to FGFR3 signalling: growth, differentiation and apoptosis. Exp. Cell Res., 304, 417-431.
81. Iwata, T., Li, C.L., Deng, C.X. and Francomano, C.A. (2001) Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice. Hum. Mol. Genet., 10, 1255-1264.
82. Coffin, J.D., Florkiewicz, R.Z., Neumann, J., Mort-Hopkins, T., Dorn, G.W. 2nd, Lightfoot, P., German, R., Howles, P.N., Kier, A., O'Toole, B.A. et al. (1995) Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. Mol. Biol. Cell, 6, 1861-1873.
83. Garofalo, S., Kliger-Spatz, M., Cooke, J.L., Wolstin, O., Lunstrum, G.P., Moshkovitz, S.M., Horton, W.A. and Yayon, A. (1999) Skeletal dysplasia and defective chondrocyte differentiation by targeted overexpression of fibroblast growth factor 9 in transgenic mice. J. Bone Miner. Res., 14, 1909-1915.
84. Koyama, E., Leatherman, J.L., Noji, S. and Pacifici, M. (1996) Early chick limb cartilaginous elements possess polarizing activity and express hedgehog-related morphogenetic factors. Dev. Dyn., 207, 344-354.
85. Wuelling, M. and Vortkamp, A. (2010) Transcriptional networks controlling chondrocyte proliferation and differentiation during endochondral ossification. Pediatr. Nephrol., 25, 625-631.
86. Beier, F., Ali, Z., Mok, D., Taylor, A.C., Leask, T., Albanese, C., Pestell, R.G. and LuValle, P. (2001) TGFbeta and PTHrP control chondrocyte proliferation by activating cyclin D1 expression. Mol. Biol. Cell, 12, 3852-3863.
87. Dailey, L., Laplantine, E., Priore, R. and Basilico, C. (2003) A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation. J. CellBiol., 161, 1053-1066.
88. Minina, E., Kreschel, C., Naski, M.C., Ornitz, D.M. and Vortkamp, A. (2002) Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev. Cell., 3, 439-449.
89. Razzaque, M.S., Soegiarto, D.W., Chang, D., Long, F. and Lanske, B. (2005) Conditional deletion of Indian hedgehog from collagen type 2alpha1-expressing cells results in abnormal endochondral bone formation. J. Pathol., 207, 453-461.
90. Orr-Urtreger, A., Givol, D., Yayon, A., Yarden, Y. and Lonai, P. (1991) Developmental expression of two murine fibroblast growth factor receptors, flg and bek. Development, 113, 1419-1434.
91. Su, N., Sun, Q., Li, C., Lu, X., Qi, H., Chen, S., Yang, J., Du, X., Zhao, L., He, Q. et al. (2010) Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis. Hum. Mol. Genet., 19, 1199-1210.
92. Contractor, T., Babiarz, B., Kowalski, A.J., Rittling, S.R., Sorensen, E.S. and Denhardt, D.T. (2005) Osteoclasts resorb protein-free mineral (Osteologic discs) efficiently in the absence of osteopontin. In Vivo, 19, 335-341.
93. Rittling, S.R., Matsumoto, H.N., McKee, M.D., Nanci, A., An, X.R., Novick, K.E., Kowalski, A.J., Noda, M. and Denhardt, D.T. (1998) Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J. Bone Miner. Res., 13, 1101-1111.
94. Chellaiah, M.A., Kizer, N., Biswas, R., Alvarez, U., Strauss-Schoenberger, J., Rifas, L., Rittling, S.R., Denhardt, D.T. and Hruska, K.A. (2003) Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol. Biol. Cell, 14, 173-189.
95. Chellaiah, M.A. and Hruska, K.A. (2003) The integrin alpha(v)beta(3) and CD44 regulate the actions of osteopontin on osteoclast motility. Calcif. Tissue Int., 72, 197-205.
96. Lanske, B., Amling, M., Neff, L., Guiducci, J., Baron, R. and Kronenberg, H.M. (1999) Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development. J. Clin. Invest., 104, 399-407.
97. Wang, W., Lian, N., Ma, Y., Li, L., Gallant, R.C., Elefteriou, F. and Yang, X. (2012) Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh. Development, 139, 601-611.
98. Elefteriou, F., Kolanczyk, M., Schindeler, A., Viskochil, D.H., Hock, J.M., Schorry, E.K., Crawford, A.H., Friedman, J.M., Little, D., Peltonen, J. et al. (2009) Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options. Am. J. Med. Genet. A, 149A, 2327-2338.
99. Stevenson, D.A., Zhou, H., Ashrafi, S., Messiaen, L.M., Carey, J.C., D'Astous, J.L., Santora, S.D. and Viskochil, D.H. (2006) Double inactivation of NF1 in tibial pseudarthrosis. Am. J. Hum. Genet., 79, 143-148.
100. Kolanczyk, M., Kossler, N., Kuhnisch, J., Lavitas, L., Stricker, S., Wilkening, U., Manjubala, I., Fratzl, P., Sporle, R., Herrmann, B.G. et al. (2007) Multiple roles for neurofibromin in skeletal development and growth. Hum. Mol. Genet., 16, 874-886.
101. Wu, X., Chen, S., He, Y., Rhodes, S.D., Mohammad, K.S., Li, X., Yang, X., Jiang, L., Nalepa, G., Snider, P. et al. (2011) The haploinsufficient hematopoietic microenvironment is critical to the pathological fracture repair in murine models of neurofibromatosis type 1. PloS ONE, 6, e24917.
102. Ovchinnikov, D.A., Deng, J.M., Ogunrinu, G. and Behringer, R.R. (2000) Col2a1-directed expression of Cre recombinase in differentiating chondrocytes in transgenic mice. Genesis, 26, 145-146.
103. Gartland, A., Mechler, J., Mason-Savas, A., MacKay, C.A., Mailhot, G., Marks, S.C. Jr and Odgren, P.R. (2005) In vitro chondrocyte differentiation using costochondral chondrocytes as a source of primary rat chondrocyte cultures: an improved isolation and cryopreservation method. Bone, 37, 530-544.
104. Boyum, A. (1968) Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand. J. Clin. Lab. Invest., 97, 77-89.
105. Masuyama, R., Stockmans, I., Torrekens, S., Van Looveren, R., Maes, C., Carmeliet, P., Bouillon, R. and Carmeliet, G. (2006) Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts. J. Clin. Invest., 116, 3150-3159.