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 p16Ink4a, 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.

中文翻译：

---

LPS 诱导的骨细胞过早衰老：炎症性牙槽骨丢失和牙周病发病机制的意义

细胞衰老与炎症和细胞外基质组织通过分泌称为衰老相关分泌表型 (SASP) 的蛋白质有关。尽管骨骼中老年人的骨细胞衰老已得到广泛认可，但年轻的肺泡骨细胞是否也会衰老尚不清楚。这在牙周病的背景下可能很重要，牙周病是一种炎症状况，由可导致牙齿脱落的共生口腔微生物群逐渐转变为致病性口腔微生物群落。我们的目的是确定衰老的骨细胞是否在年轻的牙槽骨中积累，以及细菌来源的脂多糖 (LPS) 是否会影响牙槽骨中的细胞衰老。与支管对照细胞​​相比，从牙槽骨中分离出的富含骨细胞的细胞群表达的已知衰老标记物 p16Ink4a 以及已知与牙槽骨吸收有关的精选 SASP 标记物（Icam1、Il6、Il17、Mmp13 和 Tnfα）水平升高. 使用衰老相关的卫星扩张 (SADS) 测定在体内观察到牙槽骨骨细胞衰老增加，γH2AX 增加，γH2AX 是与衰老细胞相关的 DNA 损伤的标志物。为了模拟体外细菌感染，用 LPS 处理肺泡骨细胞。我们发现各种衰老和 SASP 标志物的表达增加、γH2AX 染色增加、SA-β-Gal 活性增加以及 F-肌动蛋白的重新分布导致细胞形态学变大和变平，所有这些都是细胞衰老的标志。综上所述，