Abstract
The periodontal ligament (PDL) is a fibrous connective tissue that anchors tooth cementum into alveolar bone. Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein known to influence collagen fiber assembly in the PDL. In contrast, functional properties of the N-propeptide of collagen I, encoded in exon 2 of the COL1A1 gene, are poorly understood. In this study, the PDL of collagen I exon 2-deleted (wt/ko), SPARC-null (ko/wt), and double transgenic (ko/ko) mice were evaluated in terms of cellularity, collagen area, fiber morphology, and extraction force and compared to WT (wt/wt) mice. Picro sirius red staining indicated a decrease in total PDL collagen content in each of the transgenic mice compared to WT at 1 and 3 month age points. At 12 months, only SPARC-null (ko/wt) and double-null PDL demonstrated less total collagen versus WT. Likewise, an increase in thin PDL collagen fibers was observed at 1 and 3 months in each transgenic, with increases only in SPARC-null and double-null mice at 12 months. The force required for tooth extraction was significantly reduced in SPARC-null versus exon 2-deleted and WT mice, whereas double-null mice demonstrated further decreases in force required for tooth extraction. The number of proliferating fibroblasts and number and size of epithelial rests of Malassez were increased in each transgenic versus WT with double-null PDL exhibiting highest levels of proliferation and rests of Malassez at 1 month of age. Consistent with increases in PDL collagen in exon-2 deleted mice, with age, numbers of rests decreased at 12 months in this genotype. These results demonstrate for the first time a functional role of the N-propeptide in regulating collagen fiber assembly and cell behavior and suggest that SPARC and the N-propeptide of collagen I have distinct activities in regulating collagen fiber assembly and fibroblast function.
Highlights
Collagen type I is the main structural component of the periodontal ligament (PDL), which tethers the mineralized outer layer of tooth root cementum to underlying alveolar bone [1]
This study evaluated whether the N-propeptide of collagen I influences extracellular matrix (ECM) assembly and fibroblast proliferation in the PDL and if loss of the N-propeptide in combination with loss of Secreted protein acidic and rich in cysteine (SPARC) expression further exacerbates the defects in PDL collagen characteristic of SPARCnull PDL
The force required to extract teeth at 1 month of age was lowest in double-null mice versus that of either single transgenic or WT mice, indicating that the loss of collagen content and integrity directly correlated to a decrease in mechanical stability of the PDL
Summary
Collagen type I is the main structural component of the periodontal ligament (PDL), which tethers the mineralized outer layer of tooth root cementum to underlying alveolar bone [1]. Degradation and/or loss of collagen fibers within the PDL, a hallmark characteristic of periodontal disease, significantly increase the risk of alveolar bone resorption and eventual tooth loss [1,2,3]. Collagen I regulation and stabilization within the extracellular matrix (ECM) is critical to maintaining periodontal health. Elucidation of cellular mechanisms that control collagen incorporation and stabilization in the periodontal ECM will facilitate identification of novel targets for restoration of the periodontium and retention of alveolar bone volume and dentition, in patients suffering from severe periodontal disease. Previous studies from our laboratory show a critical role for SPARC in maintaining collagen fiber integrity in the PDL. SPARC-null (designated ko/wt in this study) mice exhibited significant decreases in total collagen as well as decreases in thick collagen fibers in the PDL at all age points [5]. These mice exhibited significant decreases in the force needed to extract individual teeth, suggesting that the reduced collagen content and changes in fiber morphology weakened the mechanical strength of the SPARC-null PDL when compared to wild type (WT, wt/wt) [2]
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