Gremlin aggravates periodontitis via activation of the nuclear factor-kappa B signaling pathway.

Abstract

Gremlin has been reported to regulate inflammation and osteogenesis. Periodontitis is a destructive disease degenerating periodontal tissues, therefore leads to alveolar bone resorption and tooth loss. Based on the importance of Gremlin's bio-activity, the aim of this study is to, in vivo and in vitro, unveil the function of Gremlin in regulating the development of periodontitis and its consequent effects on alveolar bone loss. Clinical specimens were used to determine the expression of Gremlin in periodontal tissues by immunohistochemical staining and western blot. Then utilizing the rat periodontitis model to investigate the function of gremlin-regulated nuclear factor-kappa B (NF-κB) pathway during the development of periodontal inflammation and the alveolar bone loss. Last, the regulation of the osteogenesis of human periodontal ligament stem cells (hPDLSCs) by Gremlin under inflamed condition was analyzed by alkaline phosphatase (ALP) and alizarin red staining (ARS). We found clinically and experimentally that the expression of Gremlin is markedly increased in periodontitis tissues. Interestingly, we revealed that Gremlin regulated the progress of periodontitis via regulating the activities of NF-κB pathway and interleukin-1β (IL-1β). Notably, we observed that Gremlin influenced the osteogenesis of hPDLSCs. Thus, our present study identified Gremlin as a new key regulator for development of periodontitis. Our current study illustrated that Gremlin acts as a crucial mediator and possibly serves as a potential diagnostic marker for periodontitis. Discovery of new factors involved in the pathophysiology of periodontitis could contribute to the development of novel therapeutic treatment for the disease.