The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.

中文翻译：

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VI 型胶原蛋白缺乏症导致牙周组织破坏加剧


牙周韧带 （PDL） 是位于牙槽骨和牙齿之间的纤维结缔组织，由高度专业化的细胞外基质 （ECM） 分子和负责胶原蛋白形成、免疫反应、骨骼形成和咀嚼力感觉的异质细胞群组成。VI 型胶原蛋白 （COL6） 是一种分布广泛的 ECM 分子，在肌肉、肌腱、骨骼、软骨和皮肤等各种组织的结构完整性和机械性能中起着关键作用。然而，它在 PDL 中的作用在很大程度上仍然未知。我们的研究表明，COL6 的缺乏会损害 PDL 纤维生成并加剧结扎诱导的牙周炎 （LIP） 的组织破坏。我们发现 COL6 缺陷小鼠在 LIP 中表现出骨质流失增加和 PDL 降解，并且表达高水平 Col6α2 的成纤维细胞在 ECM 组织和细胞-ECM 相互作用中起关键作用。此外，PDL 中的 COL6 缺陷导致面向炎症反应的成纤维细胞数量增加。我们还观察到，来自 PDL 的培养的 COL6 缺陷成纤维细胞表现出与胶原纤维更新和 ECM 组织以及迁移和增殖相关的基因表达降低。我们的研究结果表明，COL6 在 PDL 中起着至关重要的作用，影响纤维细胞在纤维形成中的功能并影响牙周炎的免疫反应。这些见解促进了我们对 PDL 成熟和牙周病的分子机制的理解。