Homogentisic acid induces cytoskeleton and extracellular matrix alteration in alkaptonuric cartilage,Journal of Cellular Physiology

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Homogentisic acid induces cytoskeleton and extracellular matrix alteration in alkaptonuric cartilage
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-01-20 , DOI: 10.1002/jcp.30284
Silvia Galderisi ₁ , Vittoria Cicaloni _{1,

2} , Maria S Milella ₁ , Lia Millucci ₁ , Michela Geminiani ₁ , Laura Salvini ₂ , Laura Tinti ₂ , Cristina Tinti ₂ , Otilia V Vieira ₃ , Liliana S Alves ₃ , Alvaro H Crevenna ₄ , Ottavia Spiga ₁ , Annalisa Santucci ₁

Affiliation

Alkaptonuria (AKU) is an ultra‐rare disease caused by the deficient activity of homogentisate 1,2‐dioxygenase enzyme, leading the accumulation of homogentisic acid (HGA) in connective tissues implicating the formation of a black pigmentation called “ochronosis.” Although AKU is a multisystemic disease, the most affected tissue is the articular cartilage, which during the pathology appears to be highly damaged. In this study, a model of alkaptonuric chondrocytes and cartilage was realized to investigate the role of HGA in the alteration of the extracellular matrix (ECM). The AKU tissues lost its architecture composed of collagen, proteoglycans, and all the proteins that characterize the ECM. The cause of this alteration in AKU cartilage is attributed to a degeneration of the cytoskeletal network in chondrocytes caused by the accumulation of HGA. The three cytoskeletal proteins, actin, vimentin, and tubulin, were analyzed and a modification in their amount and disposition in AKU chondrocytes model was identified. Cytoskeleton is involved in many fundamental cellular processes; therefore, the aberration in this complex network is involved in the manifestation of AKU disease.

中文翻译：

Homogentisic acid 诱导碱性尿软骨的细胞骨架和细胞外基质改变

碱酸尿症 (AKU) 是一种极罕见的疾病，由 homogentisate 1,2-双加氧酶的活性不足引起，导致结缔组织中 homogentisic acid (HGA) 的积累，这意味着形成称为“ochronosis”的黑色色素沉着。虽然 AKU 是一种多系统疾病，但受影响最严重的组织是关节软骨，在病理过程中它似乎受到了高度的破坏。在这项研究中，实现了一个碱性蛋白尿软骨细胞和软骨模型，以研究 HGA 在细胞外基质 (ECM) 改变中的作用。AKU 组织失去了由胶原蛋白、蛋白聚糖和所有表征 ECM 的蛋白质组成的结构。AKU 软骨中这种改变的原因是由于 HGA 的积累引起的软骨细胞中细胞骨架网络的退化。分析了肌动蛋白、波形蛋白和微管蛋白这三种细胞骨架蛋白，并确定了它们在 AKU 软骨细胞模型中的数量和分布的变化。细胞骨架参与许多基本的细胞过程；因此，这个复杂网络中的畸变与 AKU 疾病的表现有关。

更新日期：2021-01-20

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