Wagener Nele, Di Fazio Pietro, Böker Kai Oliver, Matziolis Georg
Department of Trauma Surgery, Orthopedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37099 Göttingen, Germany.
Department of Visceral Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstraße, 35043 Marburg, Germany.
Life (Basel). 2022 Mar 28;12(4):496. doi: 10.3390/life12040496.
Seventy million patients worldwide are suffering from epilepsy. The long-term use of antiepileptic drugs causes the alteration of the bone tissue and its metabolism, thus increasing the risk of fractures. Clinical and pre-clinical studies have highlighted conflicting data on the influence of the relatively new antiepileptic drug pregabalin (Lyrica). The objective of the present study was therefore to investigate its cytotoxicity in primary human osteoblasts (hOB). HOB and human mesenchymal stem cells (hMSC) were isolated from patients. The human osteosarcoma cells MG63 were included as established cell line. Cells were incubated with pregabalin at concentrations ranging from 0 to 40 μg/mL. Time-dependent cell proliferation was measured by automatic cell counting, and metabolism was determined by XTT assay and osseous differentiation by alkaline phosphatase (ALP) activity. Histological examinations of calcium deposit were performed with ALP, Alizarin Red, and von Kossa staining. A concentration-dependent increase in the proliferation of hOB and hMSC was observed after treatment with pregabalin. All cells showed a significant increase in cell metabolism. The osteogenic differentiation, confirmed by the increase of calcium deposit, was promoted by the administration of pregabalin. This effect was already significant at the therapeutic plasma concentration of pregabalin (10 μg/mL). In contrast to the other antiepileptic drugs, pregabalin showed no osteocatabolic effects. Conflicting in-vivo data must therefore be attributed to systemic effects of pregabalin.
全球有七千万患者患有癫痫。长期使用抗癫痫药物会导致骨组织及其代谢发生改变，从而增加骨折风险。临床和临床前研究突显了关于相对较新的抗癫痫药物普瑞巴林（乐瑞卡）影响的相互矛盾的数据。因此，本研究的目的是调查其对原代人成骨细胞（hOB）的细胞毒性。从患者中分离出hOB和人间充质干细胞（hMSC）。将人骨肉瘤细胞MG63作为已建立的细胞系纳入研究。细胞与浓度范围为0至40μg/mL的普瑞巴林一起孵育。通过自动细胞计数测量时间依赖性细胞增殖，并通过XTT测定法测定代谢，通过碱性磷酸酶（ALP）活性测定骨分化。用ALP、茜素红和冯·科萨染色法对钙沉积进行组织学检查。用普瑞巴林处理后，观察到hOB和hMSC的增殖呈浓度依赖性增加。所有细胞的细胞代谢均显著增加。普瑞巴林的给药促进了成骨分化，这通过钙沉积的增加得到证实。在普瑞巴林的治疗血浆浓度（10μg/mL）时，这种作用就已经很显著。与其他抗癫痫药物不同，普瑞巴林没有显示出骨分解代谢作用。因此，相互矛盾的体内数据必定归因于普瑞巴林的全身效应。
