title: Influence of internal fixator stiffness on murine fracture healing: two types of fracture healing lead to two distinct cellular events and FGF-2 expressions.
abstract: This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.
authors.affiliation: Department of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Ken
authors.initials: K
authors.lastname: Urabe
authors.forename: Kouji
authors.initials: K
authors.lastname: Naruse
authors.forename: Kentaroo
authors.initials: K
authors.lastname: Uchida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Minehara
authors.forename: Takeaki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Roland
authors.initials: R
authors.lastname: Steck
authors.forename: Laura
authors.initials: L
authors.lastname: Gregory
authors.forename: Martin E
authors.initials: ME
authors.lastname: Wullschleger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schuetz
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Itoman
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000378:metabolism* / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D017102:Fracture Healing / Q000502:physiology*; D016268:Internal Fixators; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016222:Fibroblast Growth Factor 2