title: Loss of scleraxis in mice leads to geometric and structural changes in cortical bone, as well as asymmetry in fracture healing.
abstract: Scleraxis (Scx) is a known regulator of tendon development, and recent work has identified the role of Scx in bone modeling. However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx green fluorescent protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, as well as callus healing response. Botulinum toxin (BTX) was used to investigate muscle unloading effects on callus shape. Scx-mutant long bones had structural and mechanical defects.Scxgene expression was elevated andbmp4was decreased at 24 h after fracture. ScxGFP+cells were localized throughout the healing callus after fracture. Scx-mutant mice demonstrated disrupted callus healing and asymmetry. Asymmetry of Scx-mutant callus was not due to muscle unloading. Wild-type littermates (age matched) served as controls. This is the first study to explore the role of Scx in cortical bone mechanics and fracture healing. Deletion of Scx during development led to altered long bone properties and callus healing. This study also demonstrated that Scx may play a role in the periosteal response during fracture healing.-McKenzie, J. A., Buettmann, E., Abraham, A. C., Gardner, M. J., Silva, M. J., Killian, M. L. Loss of scleraxis in mice leads to geometric and structural changes in cortical bone, as well as asymmetry in fracture healing.
authors.affiliation: Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: McKenzie
authors.affiliation: Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Buettmann
authors.affiliation: Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Abraham
authors.affiliation: Department of Orthopedic Surgery, Stanford University, Redwood City, California, USA; and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gardner
authors.affiliation: Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
authors.affiliation: Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA; killianm@udel.edu.|Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Killian
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002146:Bony Callus / Q000378:metabolism; D000071538:Cortical Bone / Q000293:injuries / Q000378:metabolism* / Q000502:physiology; D017102:Fracture Healing; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; C525810:Bmp4 protein, mouse; C503815:Scx protein, mouse
keywords: callus; development; skeletal repair; tendon; transcription factors