Type VI Collagen Deficiency Causes Enhanced Periodontal Tissue Destruction

• Published in: Journal of dental research Vol. 103; no. 9; pp. 878 - 888
• Main Authors: Komori, T, Kram, V, Perry, S, Pham, H T, Jani, P, Kilts, T M, Watanabe, K, Kim, D G, Martin, D, Young, M F
• Format: Journal Article
• Language: English
• Published: United States SAGE PUBLICATIONS, INC 01.08.2024
• Subjects: Alveolar bone; Alveolar Bone Loss - pathology; Animals; Bone growth; Bone loss; Bone matrix; Cell Proliferation; Collagen; Collagen (type VI); Collagen Type VI - deficiency; Collagen Type VI - genetics; Connective tissues; Disease Models, Animal; Extracellular matrix; Extracellular Matrix - metabolism; Fibrillogenesis; Fibroblasts; Gum disease; Immune response; Inflammation; Mechanical properties; Mice; Mice, Knockout; Molecular modelling; Osteogenesis; Periodontal diseases; Periodontal ligament; Periodontal Ligament - pathology; Periodontitis; Periodontitis - pathology; periodontal ligament; biomechanics; inflammation; single-cell RNAseq; bone loss; extracellular matrix
• ISSN: 0022-0345; 1544-0591; 1544-0591
• DOI: 10.1177/00220345241256306

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 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.