LPS-induced premature osteocyte senescence: Implications in inflammatory alveolar bone loss and periodontal disease pathogenesis
Open accessAbstract
Cellular senescence is associated with inflammation and extracellular matrix tissue remodeling through the secretion of proteins termed the senescence-associated secretory phenotype (SASP). Although osteocyte senescence in older individuals in the skeleton is well recognized, whether young alveolar osteocytes can also become senescent is unknown. This is potentially important in the context of periodontal disease, which is an inflammatory condition caused by a gradual change from symbiotic to pathogenic oral microflora that can lead to tooth loss. Our aim was to identify whether senescent osteocytes accumulate in young alveolar bone and whether bacterial-derived lipopolysaccharide (LPS) can influence cellular senescence in alveolar bone. An osteocyte-enriched cell population isolated from alveolar bone expressed increased levels of the known senescence marker p16 Ink4a, as well as select SASP markers known to be implicated alveolar bone resorption (Icam1, Il6, Il17, Mmp13 and Tnfα), compared to ramus control cells. Increased senescence of alveolar bone osteocytes was also observed in vivo using the senescence-associated distension of satellites (SADS) assay and increased γH2AX, a marker of DNA damage associated with senescent cells. To approximate a bacterial infection in vitro, alveolar osteocytes were treated with LPS. We found increased expression of various senescence and SASP markers, increased γH2AX staining, increased SA-β-Gal activity and the redistribution of F-actin leading to a larger and flattened cell morphology, all hallmarks of cellular senescence. In conclusion, our data suggests a model whereby bacterial-derived LPS stimulates premature alveolar osteocyte senescence, which in combination with the resultant SASP, could potentially contribute to the onset of alveolar bone loss.
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γH2AX+ BMAds are substantially increased in both AD mice and old mice compared to their respective controls.
“Immunofluorescence using the DNA damage marker γH2AX, a robust marker of senescent cells50–52, also revealed a substantial increase in γH2AX+ BMAds in both AD mice (Fig. 3q,r) and old mice (Fig. 3s,t) compared with their respective controls.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [50]
The citation is attached to the description of γH2AX as a marker, not to the citing paper’s reported increase in γH2AX+ BMAds. The Results section identifies γH2AX as a recognized marker of DNA damage and examines it alongside senescence markers in osteocytes, but does not establish it as a robust marker of senescent cells. It does not report the AD- or old-mouse BMAd comparisons. (LLM, conf=0.82)
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- Authors
- Aquino-Martinez, R., Rowsey, J. L., Fraser, D. G., Eckhardt, B. A., Khosla, S., Farr, J. N., & Monroe, D. G.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Farr, Joshua N.
- Monroe, David G.
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 132
- Pages
- 115220
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- PMC
- PMC6990876
- OpenAlex
- W2997155069
- Cited by
- 114
- References
- 49
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 19 · 2023: 17 · 2022: 12 · 2021: 17 · 2020: 10
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Jewish National Fund (R01 AG048792)
- National Institutes of Health (P01 AG004875, R01 AR068275)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- cellular senescence, senescence-associated secretory phenotype, lipopolysaccharide, alveolar bone loss, periodontal disease, p16INK4a, γH2AX, bone resorption, inflammation, extracellular matrix remodeling, actin cytoskeleton
- MeSH terms
- Aged, Humans, Lipopolysaccharides, Osteocytes, Alveolar Bone Loss, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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