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      CYLD inhibits osteoclastogenesis to ameliorate alveolar bone loss in mice with periodontitis

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          Abstract

          Periodontitis is a chronic immune inflammatory disease that can lead to the destruction and loss of the tooth‐supporting apparatus. During this process, the balance between bone absorption mediated by osteoclasts and bone formation mediated by osteoblasts is damaged. Consistent with previous studies, we observed that depletion of cylindromatosis (CYLD) resulted in an osteoporotic bone phenotype. However, the effect of CYLD deficiency on periodontitis is undetermined. Here, we investigated whether CYLD affects periodontal tissue homeostasis in experimental periodontitis in Cyld knockout (KO) mice, and we explored the underlying mechanisms. Interestingly, we discovered significant alveolar bone density loss and severely reduced alveolar bone height in Cyld KO mice with experimentally induced periodontitis. We observed increased osteoclast number and activity in both the femurs and alveolar bones, accompanied by the downregulation of osteogenesis genes and upregulation of osteoclastogenesis genes of alveolar bones in ligatured Cyld KO mice. Taken together, our findings demonstrate that the deletion of CYLD in mice plays a vital role in the pathogenesis of periodontal bone loss and suggest that CYLD might exert an ameliorative effect on periodontal inflammatory responses.

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          Most cited references39

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          Osteoclast differentiation and activation.

          Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.
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            Periodontitis: a polymicrobial disruption of host homeostasis.

            Periodontitis, or gum disease, affects millions of people each year. Although it is associated with a defined microbial composition found on the surface of the tooth and tooth root, the contribution of bacteria to disease progression is poorly understood. Commensal bacteria probably induce a protective response that prevents the host from developing disease. However, several bacterial species found in plaque (the 'red-complex' bacteria: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) use various mechanisms to interfere with host defence mechanisms. Furthermore, disease may result from 'community-based' attack on the host. Here, I describe the interaction of the host immune system with the oral bacteria in healthy states and in diseased states.
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              Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression.

              We aimed to consolidate all epidemiologic data about severe periodontitis (SP) and, subsequently, to generate internally consistent prevalence and incidence estimates for all countries, 20 age groups, and both sexes for 1990 and 2010. The systematic search of the literature yielded 6,394 unique citations. After screening titles and abstracts, we excluded 5,881 citations as clearly not relevant to this systematic review, leaving 513 for full-text review. A further 441 publications were excluded following the validity assessment. A total of 72 studies, including 291,170 individuals aged 15 yr or older in 37 countries, were included in the metaregression based on modeling resources of the Global Burden of Disease 2010 Study. SP was the sixth-most prevalent condition in the world. Between 1990 and 2010, the global age-standardized prevalence of SP was static at 11.2% (95% uncertainty interval: 10.4%-11.9% in 1990 and 10.5%-12.0% in 2010). The age-standardized incidence of SP in 2010 was 701 cases per 100,000 person-years (95% uncertainty interval: 599-823), a nonsignificant increase from the 1990 incidence of SP. Prevalence increased gradually with age, showing a steep increase between the third and fourth decades of life that was driven by a peak in incidence at around 38 yr of age. There were considerable variations in prevalence and incidence between regions and countries. Policy makers need to be aware of a predictable increasing burden of SP due to the growing world population associated with an increasing life expectancy and a significant decrease in the prevalence of total tooth loss throughout the world from 1990 to 2010.
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                Author and article information

                Contributors
                Journal
                Journal of Cellular Physiology
                Journal Cellular Physiology
                Wiley
                0021-9541
                1097-4652
                May 2023
                March 15 2023
                May 2023
                : 238
                : 5
                : 1036-1045
                Affiliations
                [1 ] Department of Endodontics and Laboratory of Stem Cells Endocrine Immunology Tianjin Medical University School of Stomatology Tianjin China
                [2 ] Department of Genetics and Cell Biology, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences Nankai University Tianjin China
                Article
                10.1002/jcp.30990
                709a4788-7df4-4303-802e-e4fa352ede9b
                © 2023

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