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Purpose This study aimed to conduct a histomorphometric analysis on the impact of varying intrusive forces on external apical root resorption (EARR) in rat molars, using an L-loop was employed to apply intrusion forces, artificially inducing EARR in the maxillary left first molar (M1) of rats.Materials and methods The L-loop was bent on a plaster rat model using stainless steel round wires with diameters of 0.014 and 0.016 inches. Using a universal test force measuring device, L-loops were calibrated to 4 N/mm and 6 N/mm for the 0.014-inch and 0.016-inch diameter stainless steel round wires, respectively. Fifteen-week-old Sprague-Dawley (SD) male rats were used and divided into the control (no loop) and experimental (0.014 and 0.016) groups (n = 5 for each group). The L-loop was attached to the left maxillary molar, applying an intrusive force to M1. After 15 days, the rats were euthanized. Maxillary bones were analysed using micro-computed tomography (μCT), evaluating M1 intrusive distance of vertical tooth movement and counting the number of tartrate-resistant acid phosphatase (TRAP)-positive cells on the surface of the mesial root apex and alveolar bone.Results The L-loop groups exhibited significantly increased M1 intrusive distance and TRAP-positive cell counts compared to controls. Specifically, the 0.016 group demonstrated greater M1 intrusive distance and more TRAP-positive cells than the 0.014 group. The M1 intrusive distance and TRAP-positive cells increased when intrusive forces were applied using L-loops of different diameters.Conclusion Greater intrusive forces enhance TRAP-positive cell activity, influencing EARR and vertical tooth movement.

Abstract In dentistry, orthodontic root resorption is a long-lasting issue with no effective treatment strategy, and its mechanisms, especially those related to senescent cells, remain largely unknown. Here, we used an orthodontic intrusion tooth movement model with an L-loop in rats to demonstrate that mechanical stress-induced senescent cells aggravate apical root resorption, which was prevented by administering senolytics (a dasatinib and quercetin cocktail). Our results indicated that cementoblasts and periodontal ligament cells underwent cellular senescence (p21+ or p16+) and strongly expressed receptor activator of nuclear factor-kappa B (RANKL) from day three, subsequently inducing tartrate-resistant acid phosphatase (TRAP)-positive odontoclasts and provoking apical root resorption. More p21+ senescent cells expressed RANKL than p16+ senescent cells. We observed only minor changes in the number of RANKL+ non-senescent cells, whereas RANKL+ senescent cells markedly increased from day seven. Intriguingly, we also found cathepsin K+p21+p16+ cells in the root resorption fossa, suggesting senescent odontoclasts. Oral administration of dasatinib and quercetin markedly reduced these senescent cells and TRAP+ cells, eventually alleviating root resorption. Altogether, these results unveil those aberrant stimuli in orthodontic intrusive tooth movement induced RANKL+ early senescent cells, which have a pivotal role in odontoclastogenesis and subsequent root resorption. These findings offer a new therapeutic target to prevent root resorption during orthodontic tooth movement.

Senescence-associated secretory phenotype (SASPs) secreted from senescent cells often cause the deleterious damages to the surrounding tissues. Although dedifferentiated fat (DFAT) cells prepared are considered a promising cell source for regenerative therapies, SASPs from DFAT cells undergoing long-term cell culture, which latently induce replicative senescence, have barely been explored. The present study was designed to investigate senescent behaviors in rat-derived DFAT cells at high passage numbers and to analyze the possible types of SASPs. Our data show that DFAT cells undergo senescence during replicative passaging, as determined by multiple senescent hallmarks including morphological changes in cell shape and nucleus. Moreover, RT2 PCR array analysis indicated that senescent DFAT cells expressed higher levels of 16 inflammatory cytokines (Ccl11, Ccl12, Ccl21, Ccl5, Csf2, Cxcl1, Cxcl12, Ifna2, IL11, IL12a, IL13, IL1a, IL1rn, IL6, Mif, and Tnf) associated with SASPs than non-senescent cells. This study implicates that rat DFAT cells undergo cellular senescence after long-term cell culture; cautious consideration should be paid to treat SASP secretion when senescent DFAT cells are used in regenerative medicine. [ABSTRACT FROM AUTHOR]