title: Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice.
abstract: Since parathyroid hormone (PTH) increased FGF2 mRNA and protein expression in osteoblasts, and serum FGF-2 was increased in osteoporotic patients treated with PTH, we assessed whether the anabolic effect of PTH was impaired in Fgf2-/- mice. Eight-week-old Fgf2+/+ and Fgf2-/- male mice were treated with rhPTH 1-34 (80mug/kg) for 4 weeks. Micro-CT and histomorphometry demonstrated that PTH significantly increased parameters of bone formation in femurs from Fgf2+/+ mice but the changes were smaller and not significant in Fgf2-/- mice. IGF-1 was significantly reduced in serum from PTH-treated Fgf2-/- mice. DEXA analysis of femurs from Fgf2+/+, Fgf2+/-, and Fgf2-/- mice treated with rhPTH (160mug/kg) for 10 days showed that PTH significantly increased femoral BMD in Fgf2+/+ by 18%; by only 3% in Fgf2+/- mice and reduced by 3% in Fgf2-/- mice. We conclude that endogenous Fgf2 is important for maximum bone anabolic effect of PTH in mice.
authors.affiliation: University of Connecticut Health Center, Farmington, CT, USA. Hurley@nso1.uchc.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Hurley
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: N
authors.initials: N
authors.lastname: Okimoto
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: C J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: T
authors.initials: T
authors.lastname: Doetschman
authors.forename: J D
authors.initials: JD
authors.lastname: Coffin
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005269:Femur / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019379:Teriparatide / Q000494:pharmacology; D014057:Tomography, X-Ray Computed
chemical_list: D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D019379:Teriparatide; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2