title: Diminished bone regeneration after debridement of posttraumatic osteomyelitis is accompanied by altered cytokine levels, elevated B cell activity, and increased osteoclast activity.
abstract: Osteomyelitis is a frequent consequence of open fractures thus representing a common bone infection with subsequent alteration of bone regeneration. Impaired bone homeostasis provokes serious variations in the bone remodeling process, thereby involving multiple inflammatory cytokines to activate bone healing. Our previously established mouse model of posttraumatic osteomyelitis provides the chance to study regulation of selected cytokines after surgical debridement of osteomyelitis thus illustrating the course of initial infectious recovery. An inflammatory cytokine array revealed specifically upregulated cytokines in debrided animals after bone infection, that were verified by Western blot analysis, identifying increased levels of CCL2, CCL3, and CXCL2. Increased osteoclastogenesis after debridement of osteomyelitis was demonstrated by Calcitonin-receptor and RANKL detection via immunohistochemical and -fluorescence stainings. The substantial protein analysis was complemented by uncovering diminished osteogenesis and proliferation in debrided group, tracking Osteocalcin, RUNX2, and PCNA expression. Interestingly TNF-α expression seemed to have no effect on altered bone regeneration after bone infection. Additional flow cytometry analysis proved elevated B cell activity, subsequently increased osteoclast activity and accelerated bone resorption. Based on the variety of severely altered cytokines, we propose a RANKL-dependent osteoclastogenesis after debridement of osteomyelitis coinciding with elevated B cells and simultaneously decreased osteogenesis. A comprehensive understanding of these mechanisms provides new therapeutic options of osteomyelitis cure and is of great importance in prospective medical treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2425-2434, 2017.
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Wagner
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Henriette
authors.initials: H
authors.lastname: Jaurich
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wallner
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Abraham
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Becerikli
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Mehran
authors.initials: M
authors.lastname: Dadras
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Kamran
authors.initials: K
authors.lastname: Harati
authors.affiliation: Institute of Immunology, University Hospital Essen, Essen, Germany.
authors.forename: Vikas
authors.initials: V
authors.lastname: Duhan
authors.affiliation: Institute of Immunology, University Hospital Essen, Essen, Germany.
authors.forename: Vishal
authors.initials: V
authors.lastname: Khairnar
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Lehnhardt
authors.affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la-camp Platz 1, 44789, Bochum, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Behr
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D001861:Bone Regeneration; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D003646:Debridement; D005260:Female; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology*; D010019:Osteomyelitis / Q000276:immunology / Q000378:metabolism* / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000150:complications
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha