Yoon Ji-Young, Baek Chul-Woo, Kim Hyung-Joon, Kim Eun-Jung, Byeon Gyeong-Jo, Yoon Ji-Uk
1Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Dental Research Institute, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam 50612 Korea.
2Department of Oral Physiology, School of Dentistry, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam 50612 Korea.
Tissue Eng Regen Med. 2018 Apr 21;15(3):333-340. doi: 10.1007/s13770-018-0116-z. eCollection 2018 Jun.
Remifentanil is commonly used in operating rooms and intensive care units for the purpose of anesthesia and sedation or analgesia. Although remifentanil may significantly affect the bone regeneration process in patients, there have been few studies to date on the effects of remifentanil on bone physiology. The purpose of this study was to investigate the effects of remifentanil on osteoclast differentiation and bone resorption. Bone marrow-derived macrophages (BMMs) were cultured for 4 days in remifentanil concentrations ranging from 0 to 100 ng/ml, macrophage colony-stimulating factor (M-CSF) alone, or in osteoclastogenic medium to induce the production of mature osteoclasts. To determine the degree of osteoclast maturity, tartrate-resistant acid phosphatase (TRAP) staining was performed. RT-PCR and western blotting analyses were used to determine the effect of remifentanil on the signaling pathways involved in osteoclast differentiation and maturation. Bone resorption and migration of BMMs were analyzed to determine the osteoclastic activity. Remifentanil reduced the number and size of osteoclasts and the formation of TRAP-positive multinuclear osteoclasts in a dose-dependent manner. Expression of c-Fos and NFATC1 was most strongly decreased in the presence of RANKL and remifentanil, and the activity of ERK was also inhibited by remifentanil. In the bone resorption assay, remifentanil reduced bone resorption and did not significantly affect cell migration. This study shows that remifentanil inhibits the differentiation and maturation of osteoclasts and reduces bone resorption.
瑞芬太尼常用于手术室和重症监护病房，用于麻醉、镇静或镇痛。尽管瑞芬太尼可能会显著影响患者的骨再生过程，但迄今为止，关于瑞芬太尼对骨生理学影响的研究很少。本研究的目的是探讨瑞芬太尼对破骨细胞分化和骨吸收的影响。将骨髓来源的巨噬细胞（BMMs）在浓度范围为0至100 ng/ml的瑞芬太尼中培养4天，单独使用巨噬细胞集落刺激因子（M-CSF），或在破骨细胞生成培养基中培养，以诱导成熟破骨细胞的产生。为了确定破骨细胞的成熟程度，进行了抗酒石酸酸性磷酸酶（TRAP）染色。采用RT-PCR和蛋白质印迹分析来确定瑞芬太尼对参与破骨细胞分化和成熟的信号通路的影响。分析BMMs的骨吸收和迁移情况，以确定破骨细胞活性。瑞芬太尼以剂量依赖的方式减少破骨细胞的数量和大小以及TRAP阳性多核破骨细胞的形成。在存在RANKL和瑞芬太尼的情况下，c-Fos和NFATC1的表达下降最为明显，并且瑞芬太尼也抑制了ERK的活性。在骨吸收试验中，瑞芬太尼减少了骨吸收，并且对细胞迁移没有显著影响。本研究表明，瑞芬太尼抑制破骨细胞的分化和成熟，并减少骨吸收。
