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Article Citation - WoS: 2Citation - Scopus: 2Cb65 and Novel Cb65 Liposomal System Suppress Mg63 and Saos-2 Osteosarcoma Cell Growth in Vitro(Taylor & Francis Ltd, 2024) Zorba, Basak Isil; Boyacioglu, Oezge; Caglayan, Tugba; Recber, Tuba; Nemutlu, Emirhan; Eroglu, Ipek; Korkusuz, PetekCurable approaches for primary osteosarcoma are inadequate and urge investigation of novel therapeutic formulations. Cannabinoid ligands exert antiproliferative and apoptotic effect on osteosarcoma cells via cannabinoid 2 (CB2) or transient receptor potential vanilloid type (TRPV1) receptors. In this study, we confirmed CB2 receptor expression in MG63 and Saos-2 osteosarcoma cells by qRT-PCR and flow cytometry (FCM), then reported the reduction effect of synthetic specific CB2 receptor agonist CB65 on the proliferation of osteosarcoma cells by WST-1 (water-soluble tetrazolium-1) and RTCA (real-time impedance-based proliferation). CB65 revealed an IC50 (inhibitory concentration) for MG63 and Saos-2 cells as 1.11 x 10(-11) and 4.95 x 10(-11) M, respectively. The specific antiproliferative effect of CB65 on osteosarcoma cells was inhibited by CB2 antagonist AM630. CB65 induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 h, respectively by FCM when applied submaximal concentration. A novel CB65 liposomal system was generated by a thin film hydration method with optimal particle size (141.7 +/- 0.6 nm), polydispersity index (0.451 +/- 0.026), and zeta potential (-10.9 +/- 0.3 mV) values. The encapsulation efficiency (EE%) of the CB65-loaded liposomal formulation was 51.12%. The CB65 and CB65-loaded liposomal formulation releasing IC50 of CB65 reduced proliferation by RTCA and invasion by scratch assay and induced late apoptosis of MG63 and Saos-2 cells, by FCM. Our results demonstrate the CB2 receptor-mediated antiproliferative and apoptotic effect of a new liposomal CB65 delivery system on osteosarcoma cells that can be used as a targeted and intelligent tool for bone tumors to ameliorate pediatric bone cancers following in vivo validation.Article Does Dexmedetomidine Induce Bone Regeneration in Cranial Defects in Rabbits(Taylor & Francis Ltd, 2025) Erkan, Gozde Nur; Tekin, Umut; Boyacioglu, Ozge; Korkusuz, Petek; Orhan, Kaan; Kirman, Betul; Onder, Mustafa ErcumentDexmedetomidine has been shown to exert protective and curative effects on various tissues and organs in different pathological processes. This study aimed to investigate the effect of dexmedetomidine on the regeneration process after making holes in the parietal bones of rabbits. Twenty-four male Oryctolagus cuniculus rabbits were allocated to three groups, and an 8-mm circular parietal critical-sized bone defect was induced in each animal. Group_C (control) received saline; Group_LD (low dose) was given dexmedetomidine 2.75 mu g/kg; Group_HD (high dose), dexmedetomidine 5.5 mu g/kg; all were administered intraperitoneally for 7 days. After 8 weeks the bones were examined by micro-computed tomography (micro-CT) and histomorphometry. The results indicated that regeneration was improved in both the dexmedetomidine-treated groups. The lower dose increased the bone volume ratio (BV/TV) more than the higher dose. Trabecular thickness, connectivity value, and connectivity density were also higher in Group_LD than in Group_HD. Significant intramembranous ossification was observed in the dexmedetomidine-treated groups, and active osteoblasts were seen at the margins of new bone trabeculae. We conclude that dexmedetomidine, especially at the lower dosage, increases osteoblastic activity and regeneration quality.
