T-lymphocytes enable osteoblast maturation via IL-17F during the early phase of fracture repair

PLoS One. 2012;7(6):e40044. doi: 10.1371/journal.pone.0040044. Epub 2012 Jun 29.


While it is well known that the presence of lymphocytes and cytokines are important for fracture healing, the exact role of the various cytokines expressed by cells of the immune system on osteoblast biology remains unclear. To study the role of inflammatory cytokines in fracture repair, we studied tibial bone healing in wild-type and Rag1(-/-) mice. Histological analysis, µCT stereology, biomechanical testing, calcein staining and quantitative RNA gene expression studies were performed on healing tibial fractures. These data provide support for Rag1(-/-) mice as a model of impaired fracture healing compared to wild-type. Moreover, the pro-inflammatory cytokine, IL-17F, was found to be a key mediator in the cellular response of the immune system in osteogenesis. In vitro studies showed that IL-17F alone stimulated osteoblast maturation. We propose a model in which the Th17 subset of T-lymphocytes produces IL-17F to stimulate bone healing. This is a pivotal link in advancing our current understanding of the molecular and cellular basis of fracture healing, which in turn may aid in optimizing fracture management and in the treatment of impaired bone healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Bony Callus
  • Cell Differentiation*
  • Cell Line
  • Cytokines / metabolism
  • Fracture Healing*
  • Gene Expression Regulation
  • Homeodomain Proteins / metabolism
  • Inflammation / pathology
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Osteoblasts / metabolism
  • Osteoblasts / pathology*
  • Osteogenesis
  • T-Lymphocytes / metabolism*


  • Biomarkers
  • Cytokines
  • Homeodomain Proteins
  • Interleukin-17
  • RAG-1 protein