PDF(Pubmed)
Abstract：
The migration of mandibular fibrochondrocytes is important for the development of the mandible, the homeostasis of the mandibular cartilage, and for the capacity of the tissue to respond to injury. Mandibular fibrochondrocytes have to overcome formidable obstacles during migration including a dense and heterogeneous three-dimensional matrix. Guiding the direction of cell migration and commitment to a migratory phenotype in this microenvironment necessitates a multivalent response to chemotactic and extracellular matrix-mediated stimuli. One of the key matrix components in the cartilage of the temporomandibular joint is type VI collagen. Neuron/glial antigen 2 (NG2/CSPG4) is a transmembrane proteoglycan that binds with collagen VI and has been implicated in a wide range of cell behaviors including cell migration, motility, adhesion, and proliferation. While NG2/CSPG4 has been shown to be a key regulator of mandibular cartilage homeostasis, its role in the migration of mandibular fibrochondrocytes during normal and cell stress conditions has yet to be resolved. Here, we address this gap in knowledge by characterizing NG2/CSPG4-dependent migration in mandibular fibrochondrocytes using primary mandibular fibrochondrocytes isolated from control and full length NG2/CSPG4 knockout mice, in primary mandibular fibrochondrocytes isolated from NG2|DsRed reporter mice and in an immortalized mandibular fibrochondrocyte cell line with a mutated NG2/CSPG4 ectodomain. All three cells demonstrate similar results, with loss of the full length or truncated NG2/CSPG4 increasing the rate of cell migration in serum starvation/cell stress conditions. These findings clearly implicate NG2/CSPG4 as a key molecule in the regulation of cell migration in mandibular fibrochondrocytes in normal and cell stress conditions, underscoring the role of NG2/CSPG4 as a mechanosensitive signaling hub in the mandibular cartilage.
摘要：
下颌骨纤维软骨细胞的迁移对下颌骨的发育至关重要，下颌软骨的稳态，以及组织对损伤的反应能力。下颌纤维软骨细胞必须克服迁移过程中的巨大障碍，包括致密且异质的三维基质。在这种微环境中指导细胞迁移的方向和对迁移表型的承诺需要对趋化性和细胞外基质介导的刺激的多价反应。颞下颌关节软骨中的关键基质组分之一是VI型胶原。神经元/神经胶质抗原2（NG2/CSPG4）是一种跨膜蛋白聚糖，与VI型胶原结合，并参与了广泛的细胞行为，包括细胞迁移，运动性,附着力,和扩散。虽然NG2/CSPG4已被证明是下颌软骨稳态的关键调节因子，它在正常和细胞应激条件下下颌纤维软骨细胞迁移中的作用尚未解决。这里,我们通过使用分离自对照和全长NG2/CSPG4敲除小鼠的原代下颌纤维软骨细胞来表征下颌纤维软骨细胞中NG2/CSPG4依赖性迁移，从而解决了这一知识空白。在从NG2|DsRed报告小鼠分离的原代下颌纤维软骨细胞和具有突变的NG2/CSPG4胞外域的永生化下颌纤维软骨细胞系中。所有三个细胞都显示出相似的结果，在血清饥饿/细胞应激条件下，全长或截短的NG2/CSPG4的丢失增加了细胞迁移的速率。这些发现清楚地表明，在正常和细胞应激条件下，NG2/CSPG4是调节下颌纤维软骨细胞迁移的关键分子。强调NG2/CSPG4作为下颌软骨中机械敏感信号传导枢纽的作用。
