MDSCs Differentiate Into Osteoclasts Induced By Porphyromonas Gingivalis Infection

Objectives: Myeloid-derived suppressor cells (MDSCs) have been shown to cause bone loss in tumor-bearing mice, it also has an expansion during bacterial infection. The mechanism of alveolar bone loss is still unclear in chronic periodontitis.As Porphyromonas gingivalis (P. gingivalis) is an important bacterium associated with periodontal disease, it is very important to determine the expansion and function of MDSCs induced by P. gingivalis and the increased osteoclasts (OC) activity.
Methods: C57BL/6 mice were infected with P. gingivalis for two weeks by a continuous infusion pump. To assess the expansion of MDSCs, spleen and bone marrow (BM) derived cells were sorted by flow cytometry for the expression of CD11b, Ly6C and Ly6G. Controls were non-infected mice. Sorted MDSCs were cultured in media containing M-CSF and RANKL respectively and OC differentiation were assessed using tartrate-resistant acid phosphatase (TRAP) staining. Additionally, the cytokines IL-10 and IFN-g from the splenocytes co-cultured with corresponding MDSCs restimulated with P. gingivalis were assessed by ELISA, the expression of NF-kB and MAPK pathway were detected by Western blot.
Results: The expansion of MDSCs induced by the exposure to P. gingivalis systemically had a bit increase. The differentiation of MDSCs showed that there was more OC formation in infected MDSCs than in naive ones. The levels of IL-10 and IFN-g from co-cultured with MDSCs increased compared with control group. The NF-kB and MAPK pathway were involved in the process.
Conclusions: The expansion and function of MDSC following exposure to P. gingivalis could differentiate into OC through NF-kB pathway.