Acid sphingomyelinase deficiency exacerbates LPS‐induced experimental periodontitis
- 28 December 2019
- journal article
- research article
- Published by Wiley in Oral Diseases
- Vol. 26 (3), 637-646
- https://doi.org/10.1111/odi.13268
Abstract
Background Mutation of the gene for acid sphingomyelinase (ASMase) causes Niemann–Pick disease. However, the effect of ASMase deficiency on periodontal health is unknown. Periodontal disease is a disease resulting from infection and inflammation of periodontal tissue and alveolar bone that support the teeth. The goal of this study was to determine the role of ASMase deficiency in periodontal inflammation and alveolar bone loss. Methods We induced periodontitis in wild‐type and ASMase‐deficient (ASMase−/−) mice with periodontal lipopolysaccharide (LPS) injection and compared the alveolar bone loss and periodontal inflammation between these mice. Results Results showed that ASMase deficiency did not significantly change metabolic parameters, but exacerbated LPS‐induced alveolar bone loss, osteoclastogenesis, and periodontal tissue inflammation. To understand the mechanisms by which ASMase deficiency aggravates LPS‐induced periodontitis, we analyzed sphingolipids in periodontal tissues. Results showed that ASMase deficiency led to increases in not only sphingomyelin, but also ceramide (CER), a bioactive sphingolipid known to promote inflammation. Results further showed that ASMase deficiency increased CER de novo synthesis. Conclusion ASMase deficiency exacerbated LPS‐induced alveolar bone loss and periodontal inflammation. ASMase deficiency leads to an unexpected CER increase by stimulating de novo synthesis CER, which is likely to be involved in the ASMase deficiency‐exacerbated periodontitis.Funding Information
- National Institute of Dental and Craniofacial Research (DE027070, DE016353)
- U.S. Department of Veterans Affairs (I01 BX000854)
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