Depletion of Gangliosides Enhances Articular Cartilage Repair in Mice.
Depletion of Gangliosides Enhances Articular Cartilage Repair in Mice.
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DOI：
10.1038/srep43729
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发表时间：
2017-03-02
影响因子：
4.6
通讯作者：
Iwasaki N
中科院分区：
文献类型：
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作者：
Matsuoka M;Onodera T;Homan K;Sasazawa F;Furukawa JI;Momma D;Baba R;Hontani K;Joutoku Z;Matsubara S;Yamashita T;Iwasaki N
阐明受损组织的愈合机制是实现组织工程突破的关键一步。关节软骨因其均匀的细胞外基质和较少的细胞类型而成为临床上用再生医学修复最成功的组织之一。然而，我们对软骨修复机制知之甚少，因此再生软骨仍然不如天然组织。在这里，我们表明糖基化是关节软骨修复过程中肥厚分化的重要过程。 GM3 是大多数神经节苷脂的前体分子，在周围受损组织中短暂表达，并且 GM3 合酶的消耗增强了软骨修复。神经节苷脂还通过印度刺猬途径调节软骨细胞肥大。这些结果确定了一种通过糖基化调节的软骨细胞肥大来实现软骨愈合的新机制。神经节苷脂及其合酶的操作可能对关节软骨修复产生有益的影响。
Elucidation of the healing mechanisms in damaged tissues is a critical step for establishing breakthroughs in tissue engineering. Articular cartilage is clinically one of the most successful tissues to be repaired with regenerative medicine because of its homogeneous extracellular matrix and few cell types. However, we only poorly understand cartilage repair mechanisms, and hence, regenerated cartilage remains inferior to the native tissues. Here, we show that glycosylation is an important process for hypertrophic differentiation during articular cartilage repair. GM3, which is a precursor molecule for most gangliosides, was transiently expressed in surrounding damaged tissue, and depletion of GM3 synthase enhanced cartilage repair. Gangliosides also regulated chondrocyte hypertrophy via the Indian hedgehog pathway. These results identify a novel mechanism of cartilage healing through chondrocyte hypertrophy that is regulated by glycosylation. Manipulation of gangliosides and their synthases may have beneficial effects on articular cartilage repair.