title: T-lymphocytes enable osteoblast maturation via IL-17F during the early phase of fracture repair.
abstract: 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.
authors: Division of Orthopaedic Surgery, Department of Surgery, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada. diane.nam@sunnybrook.ca
authors: Diane
authors: D
authors: Nam
authors: Elaine
authors: E
authors: Mau
authors: Yufa
authors: Y
authors: Wang
authors: David
authors: D
authors: Wright
authors: David
authors: D
authors: Silkstone
authors: Heather
authors: H
authors: Whetstone
authors: Cari
authors: C
authors: Whyne
authors: Benjamin
authors: B
authors: Alman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002146:Bony Callus; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D017102:Fracture Healing; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D020381:Interleukin-17 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018398:Homeodomain Proteins; D020381:Interleukin-17; C064658:RAG-1 protein