Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, V. G. Colombo 81, 20133 Milan, Italy.
IRCCS-Istituto Ortopedico Rizzoli, V. di Barbiano 1/10, 40136 Bologna, Italy.
Molecules. 2018 Dec 11;23(12):3277. doi: 10.3390/molecules23123277.
Multiple osteochondromas (MO) is a hereditary disorder associated with benign cartilaginous tumors, known to be characterized by absence or highly reduced amount of heparan sulfate (HS) in the extracellular matrix of growth plate cartilage, which alters proper signaling networks leading to improper bone growth. Although recent studies demonstrated accumulation of HS in the cytoplasm of MO chondrocytes, nothing is known on the structural alterations which prevent HS from undergoing its physiologic pathway. In this work, osteochondroma (OC), peripheral chondrosarcoma, and healthy cartilaginous human samples were processed following a procedure previously set up to structurally characterize and compare HS from pathologic and physiologic conditions, and to examine the phenotypic differences that arise in the presence of either exostosin 1 or 2 ( or ) mutations. Our data suggest that HS chains from OCs are prevalently below 10 kDa and slightly more sulfated than healthy ones, whereas HS chains from peripheral chondrosarcomas (PCSs) are mostly higher than 10 kDa and remarkably more sulfated than all the other samples. Although deeper investigation is still necessary, the approach here applied pointed out, for the first time, structural differences among OC, PCS, and healthy HS chains extracted from human cartilaginous excisions, and could help in understanding how the structural features of HS are modulated in the presence of pathological situations also involving different tissues.
多发性骨软骨瘤（MO）是一种与良性软骨肿瘤相关的遗传性疾病，其特征是生长板软骨细胞外基质中缺乏或高度减少肝素硫酸盐（HS），这会改变适当的信号网络，导致骨骼生长异常。尽管最近的研究表明 MO 软骨细胞的细胞质中 HS 的积累，但对于阻止 HS 进行其生理途径的结构改变仍一无所知。在这项工作中，对骨软骨瘤（OC）、外周软骨肉瘤和健康的人类软骨样本进行了处理，采用了先前建立的程序，以对来自病理和生理条件的 HS 进行结构表征和比较，并检查在存在外切聚糖 1 或 2（或）突变时出现的表型差异。我们的数据表明，OC 中的 HS 链主要小于 10 kDa，比健康 HS 链的硫酸化程度略高，而外周软骨肉瘤（PCSs）中的 HS 链主要大于 10 kDa，比所有其他样本的硫酸化程度都高。尽管还需要进一步深入研究，但这里应用的方法首次指出了从人软骨切除物中提取的 OC、PCS 和健康 HS 链之间的结构差异，并有助于理解 HS 的结构特征如何在涉及不同组织的病理情况下发生调节。
