title: Accelerated fracture healing in transgenic mice overexpressing an anabolic isoform of fibroblast growth factor 2.
abstract: The effect of targeted expression of an anabolic isoform of basic fibroblast growth factor (FGF2) in osteoblastic lineage on tibial fracture healing was assessed in mice. Closed fracture of the tibiae was performed in Col3.6-18 kDaFgf2-IRES-GFPsaph mice in which a 3.6 kb fragment of type I collagen promoter (Col3.6) drives the expression of only the 18 kD isoform of FGF2 (18 kDaFgf2/LMW) with green fluorescent protein-sapphire (GFPsaph) as well as Vector mice (Col3.6-IRES-GFPsaph, Vector) that did not harbor the FGF2 transgene. Radiographic, micro-CT, DEXA, and histologic analysis of fracture healing of tibiae harvested at 3, 10 and 20 days showed a smaller fracture callus but accelerated fracture healing in LMWTg compared with Vector mice. At post fracture day 3, FGF receptor 3 and Sox 9 mRNA were significantly increased in LMWTg compared with Vector. Accelerated fracture healing was associated with higher FGF receptor 1, platelet derived growth factors B, C, and D, type X collagen, vascular endothelial cell growth factor, matrix metalloproteinase 9, tartrate resistant acid phosphatase, cathepsin K, runt-related transcription factor-2, Osterix and Osteocalcin and lower Sox9, and type II collagen expression at 10 days post fracture. We postulate that overexpression of LMW FGF2 accelerated the fracture healing process due to its effects on factors that are important in chondrocyte and osteoblast differentiation and vascular invasion.
authors.affiliation: Department of Medicine, University of Connecticut School of Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
authors.forename: Marja M
authors.initials: MM
authors.lastname: Hurley
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut School of Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: Department of Craniofacial Sciences, University of Connecticut School of Dental Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Craniofacial Sciences, University of Connecticut School of Dental Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Medicine, University of Connecticut School of Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
authors.forename: Patience Meo
authors.initials: PM
authors.lastname: Burt
authors.affiliation: Department of Medicine, University of Connecticut School of Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
authors.forename: Erxia
authors.initials: E
authors.lastname: Du
authors.affiliation: Department of Medicine, University of Connecticut School of Medicine, UCONN Health, Farmington, Connecticut, 06030-052.
authors.forename: Liping
authors.initials: L
authors.lastname: Xiao
mesh_terms: D000818:Animals; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D017102:Fracture Healing; D015870:Gene Expression; D008297:Male; D008822:Mice, Transgenic; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D013977:Tibia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse
keywords: FGFR3; FRACTURE REPAIR; LMW Fgf2 ISOFORM MICE; MMP9; OSTEOCALCIN; OSTERIX; PDGF-B; PDGF-C; PDGF-D; Runx2; Sox9; VEGF