Role of Fas and Treg cells in fracture healing as characterized in the fas-deficient (lpr) mouse model of lupus.
Bottom Line: The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Fas(lpr) /J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis.B6.MRL/Fas(lpr) /J mice had elevated Treg cells in both spleens and bones of B6.MRL/Fas(lpr) /J but decreased percentage of activated T cells in bone tissues.These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process.
Affiliation: Orthopaedic Research Laboratory, Boston University School of Medicine, Boston, MA, USA; King Abdul Aziz University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Jeddah, Saudi Arabia.Show MeSH
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Mentions: To assess if the autoimmune phenotype of the B6.MRL-Faslpr/J strain affected endochondral bone formation or bone turnover during fracture healing, several different pro- and anti-inflammatory cytokines that have been shown to have altered expression during an active autoimmune state were assessed (Fig. 6A). As expected, these data showed that the expression of TNF-α, IL-1β, and IL-17F all were constitutively higher in the B6.MRL-Faslpr/J. In contrast, cytokines that would prevent the T cells from progressing to a Th1 phenotype (IL-10, IL-17A) were elevated in the mutant mice, whereas those that have been shown to inhibit Th17 development toward an iTreg (IL-6 IL-23) also showed diminished initial induction after fracture in the B6.MRL-Faslpr/J mice.(29) Using CD4 as a general assessment of T cell numbers also showed lower levels of CD4 mRNA initially after fracture in the wild-type mice. A comparison of these cytokine patterns across the time course of fracture healing further showed that there was reciprocal downregulation and upregulation of the cytokines that drive Th1 and iTreg differentiation, respectively, during the period of cartilage formation in both B6.MRL-Faslpr/J and wild-type callus tissues.
Affiliation: Orthopaedic Research Laboratory, Boston University School of Medicine, Boston, MA, USA; King Abdul Aziz University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Jeddah, Saudi Arabia.