Department of Surgery and Biomedical Sciences, Section of Obstetrics and Gynecology, University of Perugia, Perugia, Italy.
Department of Agricultural, Food and Environmental Sciences, Section of Biochemistry and Molecular Biology, University of Perugia, Perugia, Italy.
Life Sci. 2018 Sep 1;208:10-19. doi: 10.1016/j.lfs.2018.07.011. Epub 2018 Jul 7.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain and inflammation. Although it is well known that NSAIDs can suppress bone growth, remodelling and repair, they are largely used post-operatively and post-traumatically to achieve analgesia and reduce inflammation in bone tissue.
The impact of two NO-releasing, non-selective NSAIDs, NCX-4016 and HCT-3012 (NO-derivatives of Aspirin and Naproxen, respectively) on osteoblasts were evaluated and compared to the non-selective, parent chemicals and to the COX-2-selective inhibitor Celecoxib.
Using MG-63 osteoblast-like cells, we considered proliferation, the early and late stage of differentiation, and the activity of proteinases thought to be involved in osteoid degradation, a preliminary fundamental event of bone remodelling.
Unlike Aspirin, Naproxen and Celecoxib, the two NO-NSAIDs did not alter proliferation and differentiation of osteoblasts. They also reduced the activity of plasminogen activator, metalloproteinases, and cathepsin B. Similar inhibitory effects against these proteinases were recapitulated by the NO-donor sodium nitroprusside, thereby suggesting a NO-mediated mechanism.
Due to a differential effect on cell proliferation and differentiation, the two NO-NSAIDs exhibit a safer impact on osteoblast metabolism compared to Celecoxib and their parent compounds. This suggests an advantageous option for these drugs in individuals with a need of COX-inhibiting treatment, in general. In addition, their capability of modulating the proteinases involved in osteoid degradation may specifically suggest an additional safer use in comorbidity conditions of inflammation or pain with bone disorders characterized by high rate of remodelling, such as high-turnover osteoporosis in post-menopausal women.
非甾体抗炎药（NSAIDs）常用于治疗疼痛和炎症。尽管众所周知 NSAIDs 会抑制骨骼生长、重塑和修复，但它们在术后和创伤后大量用于实现骨组织的镇痛和抗炎。
评估两种释放一氧化氮的非选择性 NSAIDs（NCX-4016 和 HCT-3012，分别为阿司匹林和萘普生的 NO 衍生物）对成骨细胞的影响，并与非选择性母体药物和 COX-2 选择性抑制剂塞来昔布进行比较。
使用 MG-63 成骨样细胞，我们考虑了增殖、早期和晚期分化以及被认为参与类骨质降解的蛋白酶的活性，类骨质降解是骨重塑的初步基本事件。
与阿司匹林、萘普生和塞来昔布不同，两种 NO-NSAIDs 不会改变成骨细胞的增殖和分化。它们还降低了纤溶酶原激活物、金属蛋白酶和组织蛋白酶 B 的活性。一氧化氮供体硝普钠再现了类似的对这些蛋白酶的抑制作用，提示存在一种 NO 介导的机制。
由于对细胞增殖和分化的影响不同，与塞来昔布及其母体化合物相比，两种 NO-NSAIDs 对成骨细胞代谢的影响更安全。这表明对于需要 COX 抑制治疗的个体，这些药物是一种有利的选择。此外，它们调节参与类骨质降解的蛋白酶的能力可能特别提示在炎症或疼痛与以高重塑率为特征的骨骼疾病并存的情况下，具有更高的安全性，例如绝经后妇女的高转换骨质疏松症。
