BibTex RIS Kaynak Göster

The Role of Fibroblast Growth Factors and Bone Morfogenetik Proteins Osteogenesis

Yıl 2009, Cilt: 16 Sayı: 2, 135 - 140, 01.04.2009

Öz

Osteogenesis, which is known as the formation of bone tissue, occurs both in normal skeletal patterning during embrional period and in the recovery of bone fractures during adulthood. Although there are many factors involved in the mechanism of osteogenesis, in this study,we revised the effect of fibroblast growth factors and bone morphogenetic proteins, whose effects are further established through new studies each passing day. Key words:Osteogenesis, FGF, BMP

Kaynakça

  • Müftüoğlu S, Kaymaz F, Atilla Pergin. Netter Temel Histoloji. 2009 Sayfa: 139-41
  • Horton WA. In vitro chondrogenesis in human chondrodysplasias. Am J Med Genet 1993;45:179-82.
  • Hakkı SS, Nohutçu RM. Basik Fibroblast Growth Factor (b- FGF) ve Dexamethasone (Dex)’un pre-osteoblastların (MC3T3- E1) proliferasyonu, total protein miktarı ve hücre morfolojisi üzerine etkisi Hacettepe Dişhekimliği Fakültesi Dergisi 2005;29:/4 42-50
  • Hakkı SS, Hakkı EE, Akkaya MS. The effects of basic- fFibroblast growth factor(b-FGF) on periodontal Ligament Cells. Journal of Dental Research.2000;79: 2065
  • Çetin M, Tapan Y. b-FBF (Bazik Fibroblast Büyüme faktörü) ve formulasyonlarında yeni yaklaşımlar. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi Cilt 24;2:2004 107-24(C)
  • Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 2002;16:1446–65.
  • Iseki S, Wilkie AO, Morriss-Kay. FGFr1 and FGFr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Development 1999; 126:5611–620.
  • Shimoaka T, Ogasawara T, Yonamine A, Chikazu D, Kawano H, Nakamura K, Itoh N, Kawaguchi H Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10. J Biol Chem. 2002;277:7493–500.
  • Walsh S, Jefferiss CM, Stewart K, et al. IGF-I does not affect the proliferation or early osteogenic differentiation of human marrow stromal cells. Bone. 2003;33:80–9.
  • Fakhry A, Ratisoontorn C, Vedhachalam C, Salhab I, Koyama E, Leboy P, Pacifici M, Kirschner RE, Nah HD Effects of FBF-2/- 9 in calvarial bone cell cultures: differentiation stage-dependent mitogenic effect, inverse regulation of KMP- 2 and noggin and enhancement of osteogenic potential. Bone 2005;36:254–66.
  • Noff D, Pitaru S, Savion N. Basic fibroblast growth factor enhances the capacity of bone marrow cells to form bone-like nodules in vitro. FEBS Lett. 1989;250:619–21.
  • Pitaru S, Kotev-Emeth S, Noff D, et al. Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: enhanced development of mineralized bone- like tissue in culture. J Bone Miner Res. 1993;8:919–29.
  • Zhang X, Sobue T, Hurley MM. FGF-2 increases colony formation, PTH receptor, and IGF-1 mRNA in mouse marrow stromal cells. Biochem Biophys Res Commun. 2002;290:526–31.
  • Ducy P, Zhang R, Geoffroy V, et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997;89:747–54.
  • Ducy P, Starbuck M, Priemel M, et al. Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 1999;13:1025–36.
  • Komori T, Yagi H, Nomura S, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997;89:755–64.
  • Otto F, Thornell AP, Crompton T, et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997;89:765–71.
  • 18.Xiao G, Jiang D,Thomas P, et al. MAPK pathways activate and phosphorylate the osteoblast specific transcription factor, Cbfa1. J Biol Chem. 2000;275:4453–59.
  • Kim HJ, Lee MH, Park HS, et al. Erk pathway and activator protein 1 play crucial roles in FGF2-stimulated premature cranial suture closure. Dev Dyn 2003;227:335–46.
  • Montero A, Okada Y, Tomita M, et al. Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J Clin Invest. 2000;105:1085–93.
  • Debiais F, Debiais F, Lefèvre G, et al. Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3- kinase-dependent, -beta-catenin-independent signaling pathway. Exp. Cell Res 2004;297:235–46.
  • Ohbayashi N, Shibayama M, Kurotaki Y, et al. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002;16: 870–9.
  • Noda M, Vogel R. Fibroblast growth efector enhances type beta 1 transforming growth factor gene expression in osteoblast-like cells. J Cell Biol 1989;109:2529–35.
  • Power RA, Iwaniec UT, Wronski TJ. Changes in gene expression associated with the bone anabolic effects of basic fibroblast growth factor in aged ovariectomized rats. Bone 2002; 31;143–8.
  • Globus RK, Patterson-Buckendahl P, GospodarowiczD. Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta. Endocrinology 1988;123: 98–105.
  • Tang KT, Tang KT, Capparelli C, et al. Acidic fibroblast growth factor inhibits osteoblast differentiation in vitro: altered expression of collagenase, cell growthrelated, and mineralization- associated genes. J. Cell Biochem. 1996;61: 152–66.
  • Song H, Kwon K, Lim S, et al. Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. Mol Cells 2005;19: 402–7.
  • Zhou YX, Xu X, Chen L, et al. Pro250Arg substitution in mouse FGFR1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures. Hum Mol Gene 2000;9:2001–8.
  • Yu K, Xu J, Liu Z, et al. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth. Development. 2003; 130:3063–74.
  • Deng C, Wynshaw-Boris A, ZhouF, et al. Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell 1996;84: 911–21
  • Murakami S, Balmes G, McKinney S, et al. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the FGFR3-deficient mouse phenotype. Genes Dev. 2004;18:290–5.
  • FunatoN, Ohtani K, Ohyama K, et al. Common regulation of growth arrest and differentiation of osteoblasts by helix-loophelix factors. Mol Cell Biol. 2001;21:7416–28.
  • Valverde-Franco G, Valverde-Franco G, Liu H, et al. Defective bone mineralization and osteopenia in young adult FGFR3−/− mice. Hum Mol Genet. 2004;13:271–84.
  • Chen L, Adar R, Yang X, et al. Gly369 Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. J Clin Invest. 1999;104:1517–25.
  • Cool S, Jackson R, Pincus P, et al. Fibroblast growth factor receptor 4 (FGFR4) expression in newborn murine calvaria and primary osteoblast cultures. Int J Dev Biol. 2002; 46:519–23.
  • Burke D, Wilkes D, Blundell TL, et al. Fibroblast growth factor receptors: lessons from the genes. Trends Biochem. Sci. 1998;23:59–62.
  • Muenke M, Schell U. Fibroblast-growth-factor receptor mutations in human skeletal disorders. Trends Genet 1995;11:308–13.
  • Naski MC, Ornitz DM. FGF signaling in skeletal development. Front Biosci. 1998;3:781–94.
  • Webster MK, Donoghue DJ.FGFR activation in skeletal disorders: too much of a good thing. Trends Genet. 1997;13: 178–82.
  • Peters K, Ornitz D, Werner S, et al. Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. Dev Biol. 1993;155:423–30.
  • Dursun H. Heterotropik Ossifikasyon. FTR Bil Der J PMR Sci 2006;9:69-73
  • Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science 1988;42:1528– 34.
  • Kronenberg HM. Developmental regulation of the growth plate. Nature 2003;423:332–6.
  • Kawabata M, Miyazono K. Bone morphogenetic proteins. In: Canalis MDE (ed) skeletal growth factors. Lippincott Williams & Wilkins, Philadelphia, 2000; 269–90.
  • Miyazono K, Maeda S, Imamura T. KMP receptor signaling: transcriptional targets, regulation of signals, and signaling crosstalk. Cytokine growth factor Rev. 2005;16:251–63.
  • Karsenty G. Bone morphogenetic proteins and skeletal and nonskeletal development. In: Canalis MDE (ed) skeletal growth factors. Lippincott Williams&Wilkins, Philadelphia,2000; 291– 310.
  • Zhang H, Bradley A, at al. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 1996;122:2977–86.
  • Winnier G, Blessing M, Labosky PA, et al. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 1995;9:2105–16.
  • Daluiski A, Engstrand T, Bahamonde ME, et al. Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet 2001;27:84–8.
  • Kingsley DM, Bland AE, Grubber JM, et al. The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF beta superfamily. Cell. 1992;71:399–10.
  • Solloway MJ, Dudley AT, Bikoff EK, et al. Mice lacking KMP6 function. Dev Genet 1998;22:321–39.
  • Luo G, Hofmann C, Bronckers AL, et al. KMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 1995;9:2808–20.
  • Minina E, Kresch C, Naski MC,et al. Interaction of FGF, Ihh/Pthlh, and KMP signaling integrates Chondrocyte proliferaiton and hypertrophic differantiation. Derv Cell 2002:3:439-49.
  • Lydia Didt-Koziel, Wuelling M, Vortkamp A. Kondrogenez ve osteogenezde büyüme faktörlerinin rolü. Current Opinion in Orthopaedics Türkçe baskı.2006;4:198-207.
  • Kugimiya F, Kawaguchi H, Kamekura S, et al. Involvement of endogenous bone morphogenetic protein (BMP)2 and BMP6 in bone formation. J Biol Chem 2005;280:35704–12.
  • Cuevas P, et al. Osteopromotion for cranioplasty: an experimental study in rats using acidic fibroblast growth factor Surg Neurol. 1997;47:242–6.
  • McCracken M, Lemons JE, Zinn K. Analysis of Ti–6Al–4V implants placed with fibroblast growth factor 1 in rat tibiae. Int J Oral Maxillofac Implants. 2001;16:495–502.
  • Nakamura T, et al. Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats. Endocrinology 1995;136: 1276–84.
  • Radomsky ML, Aufdemorte TB, Swain LD, et al. Novel formulation of fibroblast growth factor-2 in a hyaluronan gel accelerates fracture healing in nonhuman primates. J Orthop Res 1999;17:607–14.
  • Govender S, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J. Bone Jt. Surg. Am. 2002;84:2123–34.

Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü

Yıl 2009, Cilt: 16 Sayı: 2, 135 - 140, 01.04.2009

Öz

Kemik dokunun oluşması olarak bilinen osteogenez, hem embriyonal dönemde normal iskelet yapısının oluşmasında hem de yetişkin dönemde kemik kırıklarının iyileşmesinde meydana gelmektedir. Osteogenez mekanizmasında pek çok faktör görev alırken bu derlemede, günümüzde, etkileri her geçen gün yeni çalışmalar ile ortaya konulan fibroblast büyüme faktörlerinin ve kemik morfogenetik proteinlerin etkisi gözden geçirilmiştir. Anahtar kelimeler:Osteogenez, Fgf, Bmp

Kaynakça

  • Müftüoğlu S, Kaymaz F, Atilla Pergin. Netter Temel Histoloji. 2009 Sayfa: 139-41
  • Horton WA. In vitro chondrogenesis in human chondrodysplasias. Am J Med Genet 1993;45:179-82.
  • Hakkı SS, Nohutçu RM. Basik Fibroblast Growth Factor (b- FGF) ve Dexamethasone (Dex)’un pre-osteoblastların (MC3T3- E1) proliferasyonu, total protein miktarı ve hücre morfolojisi üzerine etkisi Hacettepe Dişhekimliği Fakültesi Dergisi 2005;29:/4 42-50
  • Hakkı SS, Hakkı EE, Akkaya MS. The effects of basic- fFibroblast growth factor(b-FGF) on periodontal Ligament Cells. Journal of Dental Research.2000;79: 2065
  • Çetin M, Tapan Y. b-FBF (Bazik Fibroblast Büyüme faktörü) ve formulasyonlarında yeni yaklaşımlar. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi Cilt 24;2:2004 107-24(C)
  • Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 2002;16:1446–65.
  • Iseki S, Wilkie AO, Morriss-Kay. FGFr1 and FGFr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Development 1999; 126:5611–620.
  • Shimoaka T, Ogasawara T, Yonamine A, Chikazu D, Kawano H, Nakamura K, Itoh N, Kawaguchi H Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10. J Biol Chem. 2002;277:7493–500.
  • Walsh S, Jefferiss CM, Stewart K, et al. IGF-I does not affect the proliferation or early osteogenic differentiation of human marrow stromal cells. Bone. 2003;33:80–9.
  • Fakhry A, Ratisoontorn C, Vedhachalam C, Salhab I, Koyama E, Leboy P, Pacifici M, Kirschner RE, Nah HD Effects of FBF-2/- 9 in calvarial bone cell cultures: differentiation stage-dependent mitogenic effect, inverse regulation of KMP- 2 and noggin and enhancement of osteogenic potential. Bone 2005;36:254–66.
  • Noff D, Pitaru S, Savion N. Basic fibroblast growth factor enhances the capacity of bone marrow cells to form bone-like nodules in vitro. FEBS Lett. 1989;250:619–21.
  • Pitaru S, Kotev-Emeth S, Noff D, et al. Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: enhanced development of mineralized bone- like tissue in culture. J Bone Miner Res. 1993;8:919–29.
  • Zhang X, Sobue T, Hurley MM. FGF-2 increases colony formation, PTH receptor, and IGF-1 mRNA in mouse marrow stromal cells. Biochem Biophys Res Commun. 2002;290:526–31.
  • Ducy P, Zhang R, Geoffroy V, et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997;89:747–54.
  • Ducy P, Starbuck M, Priemel M, et al. Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 1999;13:1025–36.
  • Komori T, Yagi H, Nomura S, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997;89:755–64.
  • Otto F, Thornell AP, Crompton T, et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997;89:765–71.
  • 18.Xiao G, Jiang D,Thomas P, et al. MAPK pathways activate and phosphorylate the osteoblast specific transcription factor, Cbfa1. J Biol Chem. 2000;275:4453–59.
  • Kim HJ, Lee MH, Park HS, et al. Erk pathway and activator protein 1 play crucial roles in FGF2-stimulated premature cranial suture closure. Dev Dyn 2003;227:335–46.
  • Montero A, Okada Y, Tomita M, et al. Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J Clin Invest. 2000;105:1085–93.
  • Debiais F, Debiais F, Lefèvre G, et al. Fibroblast growth factor-2 induces osteoblast survival through a phosphatidylinositol 3- kinase-dependent, -beta-catenin-independent signaling pathway. Exp. Cell Res 2004;297:235–46.
  • Ohbayashi N, Shibayama M, Kurotaki Y, et al. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002;16: 870–9.
  • Noda M, Vogel R. Fibroblast growth efector enhances type beta 1 transforming growth factor gene expression in osteoblast-like cells. J Cell Biol 1989;109:2529–35.
  • Power RA, Iwaniec UT, Wronski TJ. Changes in gene expression associated with the bone anabolic effects of basic fibroblast growth factor in aged ovariectomized rats. Bone 2002; 31;143–8.
  • Globus RK, Patterson-Buckendahl P, GospodarowiczD. Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta. Endocrinology 1988;123: 98–105.
  • Tang KT, Tang KT, Capparelli C, et al. Acidic fibroblast growth factor inhibits osteoblast differentiation in vitro: altered expression of collagenase, cell growthrelated, and mineralization- associated genes. J. Cell Biochem. 1996;61: 152–66.
  • Song H, Kwon K, Lim S, et al. Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. Mol Cells 2005;19: 402–7.
  • Zhou YX, Xu X, Chen L, et al. Pro250Arg substitution in mouse FGFR1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures. Hum Mol Gene 2000;9:2001–8.
  • Yu K, Xu J, Liu Z, et al. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth. Development. 2003; 130:3063–74.
  • Deng C, Wynshaw-Boris A, ZhouF, et al. Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell 1996;84: 911–21
  • Murakami S, Balmes G, McKinney S, et al. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the FGFR3-deficient mouse phenotype. Genes Dev. 2004;18:290–5.
  • FunatoN, Ohtani K, Ohyama K, et al. Common regulation of growth arrest and differentiation of osteoblasts by helix-loophelix factors. Mol Cell Biol. 2001;21:7416–28.
  • Valverde-Franco G, Valverde-Franco G, Liu H, et al. Defective bone mineralization and osteopenia in young adult FGFR3−/− mice. Hum Mol Genet. 2004;13:271–84.
  • Chen L, Adar R, Yang X, et al. Gly369 Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. J Clin Invest. 1999;104:1517–25.
  • Cool S, Jackson R, Pincus P, et al. Fibroblast growth factor receptor 4 (FGFR4) expression in newborn murine calvaria and primary osteoblast cultures. Int J Dev Biol. 2002; 46:519–23.
  • Burke D, Wilkes D, Blundell TL, et al. Fibroblast growth factor receptors: lessons from the genes. Trends Biochem. Sci. 1998;23:59–62.
  • Muenke M, Schell U. Fibroblast-growth-factor receptor mutations in human skeletal disorders. Trends Genet 1995;11:308–13.
  • Naski MC, Ornitz DM. FGF signaling in skeletal development. Front Biosci. 1998;3:781–94.
  • Webster MK, Donoghue DJ.FGFR activation in skeletal disorders: too much of a good thing. Trends Genet. 1997;13: 178–82.
  • Peters K, Ornitz D, Werner S, et al. Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. Dev Biol. 1993;155:423–30.
  • Dursun H. Heterotropik Ossifikasyon. FTR Bil Der J PMR Sci 2006;9:69-73
  • Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science 1988;42:1528– 34.
  • Kronenberg HM. Developmental regulation of the growth plate. Nature 2003;423:332–6.
  • Kawabata M, Miyazono K. Bone morphogenetic proteins. In: Canalis MDE (ed) skeletal growth factors. Lippincott Williams & Wilkins, Philadelphia, 2000; 269–90.
  • Miyazono K, Maeda S, Imamura T. KMP receptor signaling: transcriptional targets, regulation of signals, and signaling crosstalk. Cytokine growth factor Rev. 2005;16:251–63.
  • Karsenty G. Bone morphogenetic proteins and skeletal and nonskeletal development. In: Canalis MDE (ed) skeletal growth factors. Lippincott Williams&Wilkins, Philadelphia,2000; 291– 310.
  • Zhang H, Bradley A, at al. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 1996;122:2977–86.
  • Winnier G, Blessing M, Labosky PA, et al. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 1995;9:2105–16.
  • Daluiski A, Engstrand T, Bahamonde ME, et al. Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet 2001;27:84–8.
  • Kingsley DM, Bland AE, Grubber JM, et al. The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF beta superfamily. Cell. 1992;71:399–10.
  • Solloway MJ, Dudley AT, Bikoff EK, et al. Mice lacking KMP6 function. Dev Genet 1998;22:321–39.
  • Luo G, Hofmann C, Bronckers AL, et al. KMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 1995;9:2808–20.
  • Minina E, Kresch C, Naski MC,et al. Interaction of FGF, Ihh/Pthlh, and KMP signaling integrates Chondrocyte proliferaiton and hypertrophic differantiation. Derv Cell 2002:3:439-49.
  • Lydia Didt-Koziel, Wuelling M, Vortkamp A. Kondrogenez ve osteogenezde büyüme faktörlerinin rolü. Current Opinion in Orthopaedics Türkçe baskı.2006;4:198-207.
  • Kugimiya F, Kawaguchi H, Kamekura S, et al. Involvement of endogenous bone morphogenetic protein (BMP)2 and BMP6 in bone formation. J Biol Chem 2005;280:35704–12.
  • Cuevas P, et al. Osteopromotion for cranioplasty: an experimental study in rats using acidic fibroblast growth factor Surg Neurol. 1997;47:242–6.
  • McCracken M, Lemons JE, Zinn K. Analysis of Ti–6Al–4V implants placed with fibroblast growth factor 1 in rat tibiae. Int J Oral Maxillofac Implants. 2001;16:495–502.
  • Nakamura T, et al. Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats. Endocrinology 1995;136: 1276–84.
  • Radomsky ML, Aufdemorte TB, Swain LD, et al. Novel formulation of fibroblast growth factor-2 in a hyaluronan gel accelerates fracture healing in nonhuman primates. J Orthop Res 1999;17:607–14.
  • Govender S, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J. Bone Jt. Surg. Am. 2002;84:2123–34.
Toplam 60 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Makaleler
Yazarlar

Ayşe Yıldırım Bu kişi benim

Selçuk Tunik Bu kişi benim

Çiğdem Çetin

Murat Akkuş Bu kişi benim

Yayımlanma Tarihi 1 Nisan 2009
Yayımlandığı Sayı Yıl 2009 Cilt: 16 Sayı: 2

Kaynak Göster

APA Yıldırım, A., Tunik, S., Çetin, Ç., Akkuş, M. (2009). Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü. Journal of Turgut Ozal Medical Center, 16(2), 135-140.
AMA Yıldırım A, Tunik S, Çetin Ç, Akkuş M. Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü. J Turgut Ozal Med Cent. Nisan 2009;16(2):135-140.
Chicago Yıldırım, Ayşe, Selçuk Tunik, Çiğdem Çetin, ve Murat Akkuş. “Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) Ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü”. Journal of Turgut Ozal Medical Center 16, sy. 2 (Nisan 2009): 135-40.
EndNote Yıldırım A, Tunik S, Çetin Ç, Akkuş M (01 Nisan 2009) Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü. Journal of Turgut Ozal Medical Center 16 2 135–140.
IEEE A. Yıldırım, S. Tunik, Ç. Çetin, ve M. Akkuş, “Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü”, J Turgut Ozal Med Cent, c. 16, sy. 2, ss. 135–140, 2009.
ISNAD Yıldırım, Ayşe vd. “Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) Ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü”. Journal of Turgut Ozal Medical Center 16/2 (Nisan 2009), 135-140.
JAMA Yıldırım A, Tunik S, Çetin Ç, Akkuş M. Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü. J Turgut Ozal Med Cent. 2009;16:135–140.
MLA Yıldırım, Ayşe vd. “Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) Ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü”. Journal of Turgut Ozal Medical Center, c. 16, sy. 2, 2009, ss. 135-40.
Vancouver Yıldırım A, Tunik S, Çetin Ç, Akkuş M. Osteogenezde Fibroblast Büyüme Faktörleri(Fbf) ve Kemik Morfogenetik Proteinlerin (Kmp) Rolü. J Turgut Ozal Med Cent. 2009;16(2):135-40.