title: Fibroblast growth factor-2 isoform (low molecular weight/18 kDa) overexpression in preosteoblast cells promotes bone regeneration in critical size calvarial defects in male mice.
abstract: Repair of bone defects remains a significant clinical problem. Bone morphogenetic protein 2 (BMP2) is US Food and Drug Administration-approved for fracture healing but is expensive and has associated morbidity. Studies have shown that targeted overexpression of the 18-kDa low-molecular-weight fibroblast growth factor 2 isoform (LMW) by the osteoblastic lineage of transgenic mice increased bone mass. This study tested the hypotheses that overexpression of LMW would directly enhance healing of a critical size calvarial bone defect in mice and that this overexpression would have a synergistic effect with low-dose administration of BMP2 on critical size calvarial bone defect healing. Bilateral calvarial defects were created in LMW transgenic male mice and control/vector transgenic (Vector) male mice and scaffold with or without BMP2 was placed into the defects. New bone formation was assessed by VIVA-computed tomography of live animals over a 27-week period. Radiographic and computed tomography analysis revealed that at all time points, healing of the defect was enhanced in LMW mice compared with that in Vector mice. Although the very low concentration of BMP2 did not heal the defect in Vector mice, it resulted in complete healing of the defect in LMW mice. Histomorphometric and gene analysis revealed that targeted overexpression of LMW in osteoblast precursors resulted in enhanced calvarial defect healing due to increased osteoblast activity and increased canonical Wnt signaling.
authors.affiliation: Department of Medicine (L.X., C.H.-B., M.M.H.) and Department of Reconstructive Sciences (L.C., L.K.), University of Connecticut Health Center, Farmington, Connecticut 06030; Unit of Oral and Maxillofacial Implantology (D.U.), Tsurumi University School of Dental Medicine, Yokohama 230, Japan; and Inserm U1026 (S.C.), University of Bordeaux Segalen, 33076 Bordeaux, France.
authors.forename: Liping
authors.initials: L
authors.lastname: Xiao
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ueno
authors.forename: Sylvain
authors.initials: S
authors.lastname: Catros
authors.forename: Collin
authors.initials: C
authors.lastname: Homer-Bouthiette
authors.forename: Lyndon
authors.initials: L
authors.lastname: Charles
authors.forename: Liisa
authors.initials: L
authors.lastname: Kuhn
authors.forename: Marja M
authors.initials: MM
authors.lastname: Hurley
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D012886:Skull / Q000254:growth & development*; D014057:Tomography, X-Ray Computed; D060449:Wnt Signaling Pathway; D055114:X-Ray Microtomography
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2