The decline in mesenchymal stem cell (MSC) self-renewal and function with aging contributes to diseases associated with impaired osteogenesis. MSC donor age in prolonged culture also limits the therapeutic potential of these cells for tissue engineering and regenerative medicine. Here, we demonstrate an intervention to preserve the immature state MSC and consequently maintain self-renewal and differentiation capacity during in vitro aging. We showed that blocking of phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) prevents the development of an age-related phenotype and maintains MSC morphology of early passage cells with high clonogenic frequency and enhanced proliferative capacity. MSC cultured in the presence of inhibitors of Akt or mTOR also robustly maintain their osteogenic potential, that is otherwise lost during in vitro aging. We further report that these effects may be mediated by induction of expression of pluripotency genes Nanog and Oct-4 and by the reduction in the production of cytoplasmic reactive oxygen species (ROS). Additionally, loss of Akt/mTOR and ROS was accompanied with lower levels of DNA damage. These results provide an insight into mechanisms involved in MSC aging and suggest possible interventions to maintain quiescence and function of MSC prior to in vivo transplantation or as pharmacological agents in diseases associated with loss of MSC function.
Aim The purpose of this case–control study was to compare the prevalence of apical periodontitis (AP) in patients affected by autoimmune disorders (AD) (inflammatory bowel disease [IBD], rheumatoid arthritis [RA] and psoriasis [Ps]) with the prevalence of AP in subjects without AD. The prevalences of AP in patients taking biologic medications, conventional medications and no medication were also compared. Methodology Eighty‐nine patients (2145 teeth) with AD were investigated and the control group included 89 patients (2329 teeth) with no systemic diseases. Full dental panoramic tomograms were used to determine the periapical status of the teeth. Additional variables investigated included patient's socio‐demographic characteristics, medications taken by AD patients, the decayed, missing and filled teeth (DMFT) index. The chi‐square test and logistic regression analysis were used to evaluate the correlation between AD and AP. p‐Values lower than .05 were considered to be statistically significant. Results The prevalence of AP was 89.9% in AD patients and 74.2% in control subjects (odds ratio [OR] = 3.75, p = .015). The DMFT score was found to be significantly higher in the AD group (p = .004). Patients with RA had the highest risk of being affected by AP, whereas those with IBD had the lowest risk. Multiple binary logistic regression analysis indicated that the teeth of AD patients who were not taking any medication or were being treated with biologic disease‐modifying anti‐rheumatic drugs (bDMARDs) had a higher risk of being affected by AP than did the teeth of the control subjects (OR = 1.42 and OR = 2.03, respectively; p = .010). The teeth of patients taking conventional DMARDs (cDMARDs) were less affected by AP compared with those of patients taking bDMARDs. Conclusions Patients with AD, whether treated or not with biologic medications, showed a higher prevalence of AP than did those in the control group. The DMFT index score, which was higher in AD patients compared with controls was identified as a significant predictor of AP prevalence.
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