Action of IL-1β during fracture healing

Jeffrey Lange, Anna Sapozhnikova, Chuanyong Lu, Diane Hu, Xin Li, Theodore Miclau, Ralph S. Marcucio

Research output: Contribution to journalArticle

83 Scopus citations

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-1β), on osteoblast and stem cell differentiation and on intramembranous and endochondral ossification, because IL-1β exerts effects on skeletal homeostasis and is upregulated in response to fracture. We determined that IL-1β 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-1β 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-1β receptor compared to wild-type animals. We observed subtle alterations in the healing process after administering IL-1β 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.

Original languageEnglish (US)
Pages (from-to)778-784
Number of pages7
JournalJournal of Orthopaedic Research
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

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Keywords

  • Endochondral ossification
  • Fracture healing
  • Inflammation
  • Interleukin 1 beta
  • Intramembranous ossification

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Lange, J., Sapozhnikova, A., Lu, C., Hu, D., Li, X., Miclau, T., & Marcucio, R. S. (2010). Action of IL-1β during fracture healing. Journal of Orthopaedic Research, 28(6), 778-784. https://doi.org/10.1002/jor.21061