Elmasry Shady, Asfour Shihab, de Rivero Vaccari Juan Pablo, Travascio Francesco
Department of Industrial Engineering, University of Miami, Coral Gables, FL, USA.
The Miami Project to Cure Paralysis. Department of Neurological Surgery, University of Miami, Miami, FL, USA.
Comput Biol Med. 2016 Nov 1;78:126-137. doi: 10.1016/j.compbiomed.2016.09.016. Epub 2016 Sep 22.
Insulin-like growth factor-1 (IGF-1) is well-known for upregulating cell proliferation and biosynthesis of the extracellular matrix in the intervertebral disc (IVD). Pathological conditions, such as obesity or chronic kidney disease cause IGF-1 deficiency in plasma. How this deficiency impacts disc homeostasis remains unknown. Pro-anabolic approaches for the treatment of disc degeneration based on enhancing IGF-1 bioavailability to tissue-cells are considered, but knowledge of their effectiveness in enhancing cellular anabolism of a degenerated disc is limited. In this study, we developed a computational model for disc homeostasis specifically addressing the role of IGF-1 in modulating both extracellular matrix biosynthesis and cellularity in the IVD. This model was applied to investigate how changes in IGF-1 bioavailability, namely deficiency or enhancement of growth factor, affect disc health. In this study, it was found that IGF-1 deficiency mainly affects the biosynthesis of ECM components, especially in the most external regions of the IVD such as the cartilage endplates and the outer portion of annulus fibrosus. Also, a total of three approaches for increasing IGF-1 bioavailability as a therapy for degenerated IVDs were investigated. It was found that all these strategies are only beneficial to those disc regions receiving sufficient nutritional supply (i.e., the outmost IVD regions), while they exacerbate tissue degradation in malnourished regions (i.e., inner portion of the disc). This suggests that pro-anabolic growth factor-based therapies are limited in that their success strongly depends on an adequate nutritional supply to the IVD tissue, which is not guaranteed in degenerated discs.
胰岛素样生长因子-1（IGF-1）以上调椎间盘（IVD）中的细胞增殖和细胞外基质生物合成而闻名。肥胖或慢性肾病等病理状况会导致血浆中IGF-1缺乏。这种缺乏如何影响椎间盘内环境稳定仍不清楚。基于提高IGF-1对组织细胞生物利用度的促合成代谢方法被认为可用于治疗椎间盘退变，但它们在增强退变椎间盘细胞合成代谢方面的有效性的相关知识有限。在本研究中，我们开发了一个用于椎间盘内环境稳定的计算模型，专门研究IGF-1在调节IVD中细胞外基质生物合成和细胞数量方面的作用。该模型用于研究IGF-1生物利用度的变化，即生长因子缺乏或增强，如何影响椎间盘健康。在本研究中，发现IGF-1缺乏主要影响细胞外基质成分的生物合成，尤其是在IVD最外部区域，如软骨终板和纤维环外部。此外，还研究了三种增加IGF-1生物利用度作为退变IVD治疗方法的策略。发现所有这些策略仅对那些获得足够营养供应的椎间盘区域（即IVD最外层区域）有益，而它们会加剧营养不良区域（即椎间盘内部）的组织降解。这表明基于促合成代谢生长因子的疗法存在局限性，因为它们的成功强烈依赖于IVD组织充足的营养供应，而退变椎间盘中这种供应无法保证。
