Gumustas Seyit Ali, Yilmaz İbrahim, Isyar Mehmet, Sirin Duygu Yasar, Batmaz Ahmet Guray, Ugras Ali Akin, Oznam Kadir, Ciftci Zafer, Mahirogullari Mahir
Department of General Secretariat of the Public Hospitals Union, Republic of Turkey, Ministry of Health, 59100, Tekirdag, Turkey.
Department of Pharmacovigilance, Materiovigilance and Rational Use of Drugs, Republic of Turkey, Ministry of Health, 59100, Tekirdag, Turkey.
J Orthop Surg Res. 2016 Jun 30;11(1):70. doi: 10.1186/s13018-016-0406-x.
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to relieve pain and inflammation. These NSAIDs have also analgesic effects and can be administered via oral, injectable, and topical routes. During inflammation, a number of synovial mediators and cytokines are released which decrease the pH level of the synovial fluid. Administration of acidic NSAIDs further decreases the pH levels and hence contributes to the destruction of the cartilage. To our knowledge, no cellular-based study regarding the chondrotoxicity of phenyl alkanoic acid derivatives on NSAIDs was conducted before. Thus, the aim of this pioneering study was to examine the effect of frequently prescribed NSAIDs, a phenyl alkanoic acid derivative, flurbiprofen, on the proliferation and differentiation of human primer chondrocyte cultures in vitro.
Primer chondrocyte cultures were prepared from osteochondral tissue obtained during surgery for gonarthrosis. Samples not exposed to the pharmacological agent were used as the control group. The samples were treated with 1, 10, 100, 250, 500, or 1000 μM of the agent for 24, 48, and 72 h. The cell viability, toxicity, and proliferation were assessed with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis and prechondrocytic precursor stage-specific embryonic antigen-1 (SSEA-1) expression using a commercial ELISA kit spectrophotometrically. The surface morphology of the samples in each group was compared using an inverted light microscope and an environmental scanning electron microscope (ESEM). An analysis of variance was used to compare between-group differences. Tukey's honest significant difference (HSD) method (95 % confidence interval) was used to evaluate the differences and significance in averages. The alpha significance value was considered <0.01.
Statistically significant cytotoxicity was observed in the treatment groups. NSAID had a significant negative effect on the proliferation and differentiation of chondrocytes as compared to the control group (p < 0.01).
Before administering phenyl alkanoic acid derivatives in the clinical setting, their role in suppressing the proliferation and differentiation of chondrocytes should be taken into account. Thus, caution should be given when prescribing these drugs.
非甾体抗炎药（NSAIDs）常用于缓解疼痛和炎症。这些NSAIDs也具有镇痛作用，可通过口服、注射和局部给药途径使用。在炎症过程中，会释放多种滑膜介质和细胞因子，从而降低滑液的pH值。酸性NSAIDs的使用会进一步降低pH值，进而导致软骨破坏。据我们所知，此前尚未进行过关于NSAIDs中苯烷酸衍生物软骨毒性的细胞研究。因此，这项开创性研究的目的是在体外研究常用的NSAIDs（一种苯烷酸衍生物，氟比洛芬）对人原代软骨细胞培养物增殖和分化的影响。
从膝关节骨关节炎手术中获取的骨软骨组织制备原代软骨细胞培养物。未接触药物制剂的样本用作对照组。将样本用1、10、100、250、500或1000 μM的药物处理24、48和72小时。使用MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）分析法和使用商用ELISA试剂盒通过分光光度法检测前软骨细胞前体阶段特异性胚胎抗原-1（SSEA-1）表达来评估细胞活力、毒性和增殖。使用倒置光学显微镜和环境扫描电子显微镜（ESEM）比较每组样本的表面形态。采用方差分析比较组间差异。使用Tukey's真实显著差异（HSD）方法（95%置信区间）评估平均值的差异和显著性。α显著性值设定为<0.01。
在治疗组中观察到具有统计学意义的细胞毒性。与对照组相比，NSAIDs对软骨细胞的增殖和分化具有显著的负面影响（p < 0.01）。
在临床环境中使用苯烷酸衍生物之前，应考虑它们在抑制软骨细胞增殖和分化中的作用。因此，在开具这些药物时应谨慎。
