Academic Department of Trauma & Orthopaedics, School of Medicine, University of Leeds, United Kingdom.
Academic Department of Trauma & Orthopaedics, School of Medicine, University of Leeds, United Kingdom.
Injury. 2021 Jun;52(6):1294-1299. doi: 10.1016/j.injury.2021.01.007. Epub 2021 Jan 10.
INTRODUCTION & AIMS: Non Steroidal Anti-Inflammatory drugs (NSAIDs) are potent inhibitors of post-traumatic pain. Several studies have highlighted that NSAIDs could exert a negative effect on bone healing process possibly by down-regulating chondrogenesis and endochondral ossification. The aim of the study is to explore the potential mechanism though which NSAIDs can affect chondrogenesis. M&M: Trabecular bone from the fracture site was isolated from 10 patients suffering from long bone fractures. Mesenchymal Stem Cells (MSCs) were isolated following collagenase digestion and functional assays to assess the effect of diclofenac sodium on chondrogenesis were performed. Gene expression analysis of 84 key molecules was performed.
Diclofenac sodium inhibits chondrogenic differentiation and induces a strong inhibition of prostaglandin E-2 (PGE-2) production during chondrogenic differentiation. Replenishment of PGE-2 did not reverse this negative effect. Chondrogenic inhibition is similar in cells treated only for the first week of chondrogenic differentiation or continuously for 3 weeks. Gene analysis shows a strong downregulation of TGF-β3 and FGF-1 while TNF was upregulated.
NSAIDs seem to affect the transition phase of mesenchymal stem cells towards functional chondrocytes. This effect is unrelated to the endogenous production of PGE-2. The downregulation of the expression of key molecules like TGF-β3 seem to be the underlying mechanism.
非甾体抗炎药（NSAIDs）是治疗创伤后疼痛的有效抑制剂。有几项研究强调，NSAIDs 可能通过下调软骨生成和软骨内骨化对骨愈合过程产生负面影响。本研究旨在探讨 NSAIDs 影响软骨生成的潜在机制。方法：从 10 名患有长骨骨折的患者的骨折部位分离出小梁骨。采用胶原酶消化法分离间充质干细胞（MSCs），并进行功能检测，以评估双氯芬酸钠对软骨生成的影响。对 84 个关键分子的基因表达进行分析。结果：双氯芬酸钠抑制软骨分化，并在软骨分化过程中强烈抑制前列腺素 E-2（PGE-2）的产生。补充 PGE-2 并不能逆转这种负效应。仅在软骨分化的第一周或连续 3 周治疗的细胞中，软骨抑制作用相似。基因分析显示 TGF-β3 和 FGF-1 的表达强烈下调，而 TNF 上调。结论：NSAIDs 似乎影响间充质干细胞向功能性软骨细胞的过渡阶段。这种作用与内源性 PGE-2 的产生无关。关键分子如 TGF-β3 的表达下调似乎是潜在的机制。
