Kocaoğlu Merve Hayriye, Çubukçuoğlu Deniz Günseli, Aras-Tosun Duru, Altuntaş Evrim Güneş, Tuncay Erkan
Department of Pediatric Dentistry, Faculty of Dentistry, Ankara University, Ankara, 06560, Türkiye.
Ankara University, Stem Cell Institute, Ankara, 06520, Türkiye.
BMC Musculoskelet Disord. 2025 Apr 2;26(1):319. doi: 10.1186/s12891-025-08555-6.
Osteomyelitis involves bone destruction, impaired bone formation, and systemic inflammation. Dexmedetomidine (DXMT) possesses antioxidant, anti-inflammatory, and anti-apoptotic properties alongside sedative and analgesic effects. This study evaluates DXMT's effects on markers of infection and bone healing using osteocyte-like cells infected by Staphylococcus aureus (S. aureus).
Human osteosarcoma-derived SAOS-2 cells were differentiated to an osteocyte-like phenotype over 28 days using potassium dihydrogen phosphate. Differentiation was verified via qPCR for osteogenic markers. Cytotoxicity of DXMT (0.1-10 µM) was tested using WST-1 assay and Reactive Oxygen Species (ROS) production analysis. Cells infected with S. aureus were treated with DXMT to assess its antimicrobial, anti-inflammatory (via ELISA for cytokines IL1-ß, TNF-⍺, IL-17, and IL-6), and osteogenesis-promoting effects.
DXMT ≤ 1 µM did not affect cell viability, while 2, 5, and 10 µM DXMT administration reduced cell counts. A 5 µM dose slightly reduced intracellular bacterial load (6.2 log in controls vs. 6.1 log with DXMT), while neither less nor more DXMT was effective on reducing the S. aureus load. Doses ≥ 5 µM effectively reduced ROS production and inflammation post-infection in a time-dependent manner. S. aureus infection decreased osteogenic markers, but DXMT mitigated cellular stress and inflammation with a positive impact on osteogenesis at therapeutic doses.
DXMT at 5 µM is an optimal dose to reduce infection-induced cellular stress and promote bone healing in osteomyelitis in vitro, balancing antimicrobial effects and cytotoxicity.
骨髓炎涉及骨破坏、骨形成受损和全身炎症。右美托咪定（DXMT）具有抗氧化、抗炎和抗凋亡特性，同时还具有镇静和镇痛作用。本研究使用受金黄色葡萄球菌（S. aureus）感染的骨细胞样细胞评估DXMT对感染标志物和骨愈合的影响。
使用磷酸二氢钾在28天内将人骨肉瘤来源的SAOS-2细胞分化为骨细胞样表型。通过对成骨标志物进行qPCR验证分化情况。使用WST-1测定法和活性氧（ROS）产生分析测试DXMT（0.1 - 10 μM）的细胞毒性。用DXMT处理感染金黄色葡萄球菌的细胞，以评估其抗菌、抗炎（通过ELISA检测细胞因子IL1-β、TNF-α、IL-17和IL-6）和成骨促进作用。
DXMT≤1 μM不影响细胞活力，而给予2、5和10 μM DXMT会减少细胞计数。5 μM剂量略微降低了细胞内细菌载量（对照组为6.2 log，DXMT处理组为6.1 log），而DXMT剂量更低或更高对降低金黄色葡萄球菌载量均无效。≥5 μM的剂量能以时间依赖性方式有效降低感染后的ROS产生和炎症。金黄色葡萄球菌感染降低了成骨标志物，但DXMT在治疗剂量下减轻了细胞应激和炎症，对成骨有积极影响。
5 μM的DXMT是在体外减少感染诱导的细胞应激并促进骨髓炎骨愈合的最佳剂量，可平衡抗菌作用和细胞毒性。
