Senescent cells exacerbate chronic inflammation and contribute to periodontal disease progression in old mice
Open accessAbstract
Background: Coinciding with other chronic comorbidities, the prevalence of periodontal disease increases with aging. Mounting evidence has established that senescent cells accumulate at sites of age‐related pathologies, where they promote “non‐microbial” inflammation. We hypothesized that alveolar bone osteocytes develop senescence characteristics in old age. Methods: Alveolar bone samples were obtained from young (6 months) and old (20 to 22 months) mice to evaluate the expression of senescence biomarkers by immunofluorescent staining. Osteocyte‐enriched fractions were used to characterize the age‐related senescence‐associated secretory phenotype (SASP) gene expression profile. Primary alveolar bone cells were exposed to the SASP via in vitro senescent conditioned media (SCM) administration. A multiplex assay confirmed protein levels of specific cytokines. Interactions with bacterial components were evaluated by stimulating cells with lipopolysaccharide (LPS). Results: Increased senescence‐associated distension of satellites (SADS) and p16 Ink4a mRNA expression were identified in alveolar bone osteocytes with aging. These findings were associated with increased levels of DNA damage, and activated p38 MAPK, both inducers of senescence. Furthermore, interleukin‐6 (IL6), IL17, IGFBP4, and MMP13 were significantly upregulated with aging in osteocyte‐enriched samples. Interestingly, SCM potentiated the LPS‐induced expression of IL1α, IL1β, and IL6. Cell migration and differentiation were also impeded by SCM. These in vitro effects were ameliorated by the p38 MAPK inhibitor SB202190. Conclusions: Accumulation of senescent osteocytes contributes to deterioration of the periodontal environment by exacerbating chronic inflammation and reducing regeneration in old age. Cellular senescence is a cell‐intrinsic response to DNA damage, and a host‐related mechanism associated with aging that could potentiate inflammation induced by bacterial components.
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TNF-α has a stimulating effect on bone resorption but an inhibitory effect on bone formation.
“TNF-α, such as IL-6, has a stimulating effect on bone resorption but an inhibitory effect on bone formation [84, 85]”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [85]
The Results section reports that senescent osteocyte-associated factors and LPS impaired osteoblast differentiation and mineralization, but does not identify TNF-α as the cause. Searches for TNF-α and tumor necrosis factor found no passage in our copy addressing its effects on either bone resorption or bone formation. (LLM, conf=0.76)
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- Authors
- Aquino‐Martinez, R., Eckhardt, B. A., Rowsey, J. L., Fraser, D. G., Khosla, S., Farr, J. N., & Monroe, D. G.
- Affiliations
- Department of Medicine Division of Endocrinology Mayo Clinic College of Medicine Rochester MN
- Mayo Clinic (US)
- Corresponding author
- Farr, Joshua N.
- Monroe, David G.
- Venue
- Journal of Periodontology
- Publisher
- Wiley
- Published
- 2021-01-06
- Volume
- 92
- Issue
- 10
- Pages
- 1483-1495
- ISSN
- 0022-3492 (ISSN-L)
- 1943-3670
- PMC
- PMC8281492
- OpenAlex
- W3115619245
- Cited by
- 78
- References
- 52
- Citations by year
- 2026: 20 · 2025: 15 · 2024: 17 · 2023: 15 · 2022: 9 · 2021: 2
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Periodontology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG063707, R21AG065868, P01AG062413)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK128552)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR068275, K01AR070241)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- cellular senescence, periodontal disease, chronic inflammation, osteocytes, alveolar bone, aging, senescence-associated secretory phenotype, p38 MAPK, DNA damage, lipopolysaccharide, interleukin-6, IL-17, IGFBP-4, MMP-13, periodontal regeneration
- MeSH terms
- Aging, Animals, Inflammation, Osteocytes, Periodontal Diseases, Cellular Senescence, Disease Progression, Mice
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