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RESEARCH PRODUCT

Regulation of ghrelin receptor by microbial and inflammatory signals in human osteoblasts

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Made available in DSpace on 2019-10-06T16:29:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-25. Added 1 bitstream(s) on 2019-10-09T18:35:25Z : No. of bitstreams: 1 S1806-83242019000100221.pdf: 2536737 bytes, checksum: 9a25b4f5849a4b7f35298e8e3e000889 (MD5) Recently, it has been suggested that the anti-inflammatory hormone ghrelin (GHRL) and its receptor GHS-R may play a pivotal role in periodontal health and diseases. However, their exact regulation and effects in periodontitis are not known. The aim of this in-vitro study was to investigate the effect of microbial and inflammatory insults on the GHS-R1a expression in human osteoblast-like cells. MG-63 cells were exposed to interleukin (IL)-1β and Fusobacterium nucleatum in the presence and absence of GHRL for up to 2 d. Subsequently, gene expressions of GHS-R1a, inflammatory mediators and matrix metalloproteinase were analyzed by real-time PCR. GHS-R protein synthesis and NF-κB p65 nuclear translocation were assessed by immunocytochemistry and immunofluorescence microscopy, respectively. IL-1β and F. nucleatum caused a significant upregulation of GHS-R1a expression and an increase in GHS-R1a protein. Pre-incubation with a MEK1/2 inhibitor diminished the IL-1β-induced GHS-R1a upregulation. IL-1β and F. nucleatum also enhanced the expressions of cyclooxygenase 2, CC-chemokine ligand 2, IL-6, IL-8, and matrix metalloproteinase 1, but these stimulatory effects were counteracted by GHRL. By contrast, the stimulatory actions of IL-1β and F. nucleatum on the GHS-R1a expression were further enhanced by GHRL. Our study provides original evidence that IL-1β and F. nucleatum regulate the GHS-R/GHRL system in osteoblast-like cells. Furthermore, we demonstrate for the first time that the proinflammatory and proteolytic actions of IL-1β and F. nucleatum on osteoblast-like cells are inhibited by GHRL. Our study suggests that microbial and inflammatory insults upregulate GHS-R1a, which may represent a protective negative feedback mechanism in human bone. University of Bonn Center of Dento-Maxillo-Facial Medicine Section of Experimental Dento-Maxillo-Facial Medicine University Medical Center Johannes Gutenberg University Department of Periodontology and Operative Dentistry University of Bonn Center of Dento-Maxillo-Facial Medicine Department of Orthodontics University of Bern Department of Periodontology Laboratory of Oral Microbiology Universidade Estadual Paulista - UNESP School of Dentistry of Araraquara Department of Diagnosis and Surgery Universidade Estadual Paulista - UNESP School of Dentistry of Araraquara Department of Diagnosis and Surgery