Periodontitis and Mechanical Forces Modulate Ghrelin Receptor in Periodontal Tissues

Ghrelin signaling, mediated by the growth hormone secretagogue receptor (GHS-R1a), has emerged as an important regulator of inflammation and bone metabolism. This study investigated GHS-R1a regulation in periodontal tissues exposed to experimental periodontitis (EP), orthodontic tooth movement (OTM), or both. Human periodontal fibroblasts were stimulated with Fusobacterium nucleatum, static tensile strain, or their combination, and GHS-R1a expression was evaluated by RT-qPCR. In vivo experiments were conducted in rats subjected to EP, OTM, or combined treatment. Gingival GHS-R1a expression was assessed by RT-qPCR and immunohistochemistry, while alveolar bone loss was quantified histometrically. Combined bacterial and mechanical stimulation markedly increased GHS-R1a expression in periodontal fibroblasts, whereas either stimulus alone produced minimal changes. Similarly, combined EP and OTM induced a pronounced early increase in gingival GHS-R1a gene and protein expression, which declined over time. Animals exposed to both conditions also exhibited significantly greater alveolar bone loss. These findings demonstrate that periodontal inflammation and orthodontic loading dynamically regulate GHS-R1a, with early upregulation followed by attenuation during prolonged inflammation. The ghrelin/GHS-R1a system may therefore contribute to the periodontal response to concurrent inflammatory and biomechanical stimuli and participate in maintaining tissue homeostasis under inflammatory stress.