Colony‐stimulating factor‐1 receptor blockade attenuates inflammation in inflamed gingival tissue explants

Abstract

Background and objective Colony‐stimulating factor‐1 receptor (CSF‐1R) regulates myeloid cell function and mediates osteoclastogenesis. CSF‐1R blockade has been suggested as a potential therapeutic target to halt inflammation and bone resorption; however, the expression and function of CSF‐1R in human gingiva is yet unknown. Methods Gingival tissue was collected from 22 non‐periodontitis controls and 31 periodontitis (PD) patients. CSF‐1R expression in gingival tissue was assessed with q‐PCR, western blot, and immunohistochemistry (IHC). Cell surface expression of CSF‐1R was analyzed by flow cytometry. The effects of CSF‐1R inhibition on the production of inflammatory mediators by inflamed gingival tissue explants and peripheral blood mononuclear cells (PBMCs) were assessed with a bead‐based multiplex array and ELISA. Results CSF‐1R protein expression was increased in gingival tissue from PD patients compared with controls as assessed with western blot (1.5‐fold increase) and IHC (4.5‐fold increase). Similar proportions of HLA‐DR+CD64+ cells and comparable CSF‐1R expression in this cell population were found in gingival tissue from PD patients and controls. In peripheral blood monocytes, CSF‐1R was predominantly expressed by non‐classical and intermediate monocytes. Targeting CSF‐1R in gingival tissue explants attenuated the production of MMP‐1, MMP‐2, MMP‐12, and MMP‐13. The blocking in PBMCs attenuated the production of IL‐8 and MMP‐9. Conclusion These results indicate that CSF‐1R is elevated in PD, and its inhibition attenuates inflammatory mediators in the inflamed gingival tissue and circulating myeloid cells. Together these findings suggest that CSF‐1R might be involved in regulating inflammatory processes in PD, and a potential therapeutic target to reduce the harmful inflammation.

Interleukin‐34 permits Porphyromonas gingivalis survival and NF‐κB p65 inhibition in macrophages

“…Macrophages have an important role in periodontal disease, not only for controlling periodontal pathogens such as P. gingivalis but also in the pathology of the disease, including the bone loss seen during severe periodontal disease (Lam et al, 2014). The receptor CSF1R is also known to be important in driving gingival inflammation (Clark et al, 2021). Lundberg, 2013).…”

Immune Response Serves as a Bridge between Abnormal Lipid and Bone Metabolism: A Differential Expression Genes Profile Analysis Based on Clinical Data-mining

“…CSF1R regulates the function of bone marrow cells and mediates osteoclastogenesis (Kimura et al, 2014). Also, CSF1R was reported to modulate the in ammatory process linked with periodontitis (Clark et al, 2021), wherein it could reduce the in ammatory mediators in cycling bone marrow cells and gingival tissues. In an in vivo acute stress model based on LPS, CSF1R inhibitor was found to alleviate neuroin ammation of the tested animals.…”