Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) Ameliorates the Inflammatory Response in Periodontal Disease

• Published in: Inflammation Vol. 42; no. 4; pp. 1170 - 1178
• Main Authors: Song, Rong, Lin, Lexun
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2019; Springer Nature B.V
• Subjects: Alveolar bone; Anti-Inflammatory Agents; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Bone resorption; Cells, Cultured; Glycoproteins; Gum disease; Humans; Immunohistochemistry; Immunology; Inflammation - etiology; Interleukin 10; Interleukin-6 - metabolism; Internal Medicine; Lipopolysaccharides; Lysine; Melanoma; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - pharmacology; Mineralization; Original Article; Osteoblasts; Pathogenesis; Pathology; Periodontal diseases; Periodontal Diseases - metabolism; Periodontal Diseases - pathology; Periodontal ligament; Periodontal Ligament - cytology; Periodontal Ligament - drug effects; Pharmacology/Toxicology; Protein B; Proteins; Rheumatology; Teeth; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; inflammatory cytokine; Jmjd3; GPNMB; periodontal disease
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-019-00977-4

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein that can modulate osteoblasts and bone mineralization. Periodontal disease (PD) is characterized by gum inflammation, alveolar bone resorption, and tooth loss. In this study, we found that GPNMB is highly expressed in inflamed periodontal tissue through microarray and immunohistochemistry (IHC) assays. The role of GPNMB in the pathogenesis of PD was evaluated with primary human periodontal ligament cells (hPDLCs) treated with lipopolysaccharide (LPS) and a GPNMB-expressing lentivirus (lenti-GP). In the hPDLCs treated with LPS and lenti-GP, the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 was suppressed and that of IL-10 was upregulated. GPNMB significantly decreased apoptosis in the hPDLCs treated with LPS. GPNMB could upregulate the expression of Jumonji domain-containing protein 3 (Jmjd3), a histone 3 lysine 27 (H3K27) demethylase that is linked to the modulation of the inflammatory response and apoptosis. Taken together, our data find that GPNMB is highly expressed in gum tissue with PD and may be an anti-inflammatory player in the pathogenesis of PD.