title: Inflammatory phase of bone healing initiates the regenerative healing cascade.
abstract: Bone healing commences with an inflammatory reaction which initiates the regenerative healing process leading in the end to reconstitution of bone. An unbalanced immune reaction during this early bone healing phase is hypothesized to disturb the healing cascade in a way that delays bone healing and jeopardizes the successful healing outcome. The immune cell composition and expression pattern of angiogenic factors were investigated in a sheep bone osteotomy model and compared to a mechanically-induced impaired/delayed bone healing group. In the impaired/delayed healing group, significantly higher T cell percentages were present in the bone hematoma and the bone marrow adjacent to the osteotomy gap when compared to the normal healing group. This was mirrored in the higher cytotoxic T cell percentage detected under delayed bone healing conditions indicating longer pro-inflammatory processes. The highly activated periosteum adjourning the osteotomy gap showed lower expression of hematopoietic stem cell markers and angiogenic factors such as heme oxygenase and vascular endothelial growth factor. This indicates a deferred revascularization of the injured area due to ongoing pro-inflammatory processes in the delayed healing group. Results from this study suggest that there are unfavorable immune cells and factors participating in the initial healing phase. In conclusion, identifying beneficial aspects may lead to promising therapeutical approaches that might benefit further by eliminating the unfavorable factors.
authors.affiliation: Julius Wolff Institut and Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt-Bleek
authors.forename: Hanna
authors.initials: H
authors.lastname: Schell
authors.forename: Norma
authors.initials: N
authors.lastname: Schulz
authors.forename: Paula
authors.initials: P
authors.lastname: Hoff
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Jasmin
authors.initials: J
authors.lastname: Lienau
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D001861:Bone Regeneration; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D003602:Cytotoxicity, Immunologic; D005260:Female; D006406:Hematoma / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D007249:Inflammation / Q000473:pathology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology; D010027:Osteotomy; D010521:Periosteum / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D012038:Regeneration / Q000502:physiology*; D012756:Sheep; D013601:T-Lymphocytes / Q000473:pathology; D014945:Wound Healing
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers