title: Action of IL-1beta during fracture healing.
abstract: After bone injury, developmental processes such as endochondral and intramembranous ossification are recapitulated as the skeleton regenerates. In contrast to development, skeletal healing involves inflammation. During the early stages of healing a variety of inflammatory cells infiltrate the injured site, debride the wound, and stimulate the repair process. Little is known about the inflammatory process during bone repair. In this work, we examined the effect of a pro-inflammatory cytokine, Interleukin-1 beta (IL-1beta), on osteoblast and stem cell differentiation and on intramembranous and endochondral ossification, because IL-1beta exerts effects on skeletal homeostasis and is upregulated in response to fracture. We determined that IL-1beta stimulated proliferation of osteoblasts and production of mineralized bone matrix, but suppressed proliferation and inhibited differentiation of bone marrow derived MSCs. We next performed loss- and gain-of-function experiments to determine if altering IL-1beta signaling affects fracture healing. We did not detect any differences in callus, cartilage, and bone matrix production during healing of nonstabilized or stabilized fractures in mice that lacked the IL-1beta receptor compared to wild-type animals. We observed subtle alterations in the healing process after administering IL-1beta during the early phases of repair. At day 10 after injury, the ratio of cartilage to callus was increased, and by day 14, the proportion of cartilage to total callus and to bone was reduced. These changes could reflect a slight acceleration of endochondral ossification, or direct effects on cartilage and bone formation.
authors.affiliation: Department of Orthopaedic Surgery, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lange
authors.forename: Anna
authors.initials: A
authors.lastname: Sapozhnikova
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Lu
authors.forename: Diane
authors.initials: D
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Theodore
authors.initials: T
authors.lastname: Miclau
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Marcucio
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D017102:Fracture Healing / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction; D013978:Tibial Fractures / Q000503:physiopathology
chemical_list: D053583:Interleukin-1beta