Humans ; Orthodontics, Corrective ; adverse effects ; Risk Factors ; Root Resorption ; etiology ; prevention & control ; Temporomandibular Joint Disorders ; etiology ; prevention & control

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.
Rats ; Animals ; Root Resorption/prevention & control* ; Senotherapeutics ; Stress, Mechanical ; Dasatinib/pharmacology* ; Quercetin/pharmacology* ; Osteoclasts ; Tooth Movement Techniques ; Periodontal Ligament ; RANK Ligand

OBJECTIVETo compare the effects of pamidronate and ibandronate on orthodontic root resorption.

METHODSSeventy-two 6-week-old female specific pathogen free (SPF) Wistar rats were selected to establish models for orthodontic tooth movement. The rats were randomly divided into three groups: the control group (C group), pamidronate group (Pm group) and ibandronate group (Ib group). 0.9% normal saline,0.5 mmol/L pamidronate and 0.5 mmol/L ibandronate were injected every 3 days. The rats were executed in batch on the 3rd, 7th and 14th day to make tissue sections. All statistical analysis was performed using the PASW Statistics 18 software package.

RESULTSOn the 7th and 14th day, the amount of cementoclast, the expression of osteoclast differentiation factor (ODF) and root resorption index were significantly lower in Pm group [the 7th day: (2.675 ± 0.002), (0.1683 ± 0.0007), (0.103 ± 0.003); the 14th day: (3.886 ± 0.048), (0.1873 ± 0.0014), (0.283 ± 0.001)] and Ib groups[the 7th day: (2.601 ± 0.001), (0.1634 ± 0.0010), (0.099 ± 0.002); the 14th day: (3.754 ± 0.019), (0.1818 ± 0.0016), (0.281 ± 0.001)] than in C group[the 7th day: (2.810 ± 0.001), (0.1792 ± 0.0008), (0.120 ± 0.001); the 14th day: (4.800 ± 0.001), (0.2060 ± 0.0007), (0.401 ± 0.001)] (P < 0.05). However, no significant difference was found between Pm and Ib groups on the 3rd, 7th and 14th day (P > 0.05).

CONCLUSIONSBoth pamidronate and ibandronate could inhibit orthodontic root resorption.

Animals ; Bone Density Conservation Agents ; pharmacology ; Cell Count ; Diphosphonates ; pharmacology ; Female ; Osteoclasts ; cytology ; drug effects ; metabolism ; RANK Ligand ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Root Resorption ; pathology ; prevention & control ; Tooth Movement Techniques