Strontium ranelate (SR) is a pharmaceutical agent used for the prevention and treatment of osteoporosis and fragility fracture. However, little attention has been paid to the effect of SR on alveolar bone remodeling during orthodontic tooth movement and its underlying mechanism. Here, we investigated the influence of SR on orthodontic tooth movement and tooth resorption in Sprague–Dawley rats and the relationship between the nuclear factor–kappa B (NF-κB) pathway, autophagy, and osteoclastogenesis after the administration of SR in vitro and in vivo. In this study, it was found that SR reduced the expression of autophagy-related proteins at the pressure side of the first molars during orthodontic tooth movement. Similarly, the expression of these autophagy-related proteins and the size and number of autophagosomes were downregulated by SR in vitro. The results also showed that SR reduced the number of osteoclasts and suppressed orthodontic tooth movement and root resorption in rats, which could be partially restored using rapamycin, an autophagy inducer. Autophagy was attenuated after pre-osteoclasts were treated with Bay 11-7082, an NF-κB pathway inhibitor, while SR reduced the expression of the proteins central to the NF-κB pathway. Collectively, this study revealed that SR might suppress osteoclastogenesis through NF-κB-pathway-dependent autophagy, resulting in the inhibition of orthodontic tooth movement and root resorption in rats, which might offer a new insight into the treatment of malocclusion and bone metabolic diseases.

Recent therapeutic advances have improved the survival of head and neck squamous cell carcinoma (HNSCC) patients, but the prognosis of HNSCC remains dismal. Further understanding of the underlying mechanism of HNSCC progression is still an urgent need. In this study, bioinformatics-based analysis revealed that Chaperonin containing TCP-1, subunit 2 (CCT2) is significantly upregulated in HNSCC and related to pathoclinical outcomes, which is validated by the fact that four human HNSCC cell lines all express higher CCT2 than the normal oral squamous cell line. Clinically, high CCT2 expression was positively associated with worse overall survival (OS) and TNM classification in HNSCC patients. Further study indicated that suppression of CCT2 by RNA interference significantly inhibits cell proliferation, migration and invasion, arrests cell cycle at G2 phase, and prevents epithelial-mesenchymal transition (EMT) of both SAS and HSC-3 cell lines. In vivo assays further verified that CCT2 knockdown inhibited tumor growth in HNSCC. Moreover, knockdown of CCT2 led to the significant decrease of Cdc20 as well as cyclin D1, cyclin E1, and CDK6 while increase of GSK3-α/β and p27, which shed light into molecular mechanism of CCT2 function. In conclusion, elevated CCT2 expression promotes HNSCC cell proliferation via Cdc20 mediated cyclin-CDK pathway and CCT2 would be a valuable prognostic biomarker and therapeutic target in HNSCC.