Abstract
After injury to periodontal tissues, a sequentially phased healing response is initiated that enables wound closure and partial restoration of tissue structure and function. Wound closure in periodontal tissues involves the tightly regulated coordination of resident cells in epithelial and connective tissue compartments. Multiple cell populations in these compartments synergize their metabolic activities to reestablish a mucosal seal that involves the underlying periodontal connective tissues and the attachment of these tissues to the tooth surface. The formation of an impermeable seal around the circumference of the tooth is of particular significance in oral health since colonization of tooth surfaces by pathogenic biofilms promotes inflammation, which can contribute to periodontal tissue degradation and tooth loss. The reformation of periodontal tissue structures in the healing response centrally involves fibroblasts, which synthesize and organize the collagen fibers that link alveolar bone and gingiva to the cementum covering the tooth root. The synthesis and remodeling of nascent collagen matrices are of fundamental importance for the reestablishment of a functional periodontium and are mediated by diverse, multi-functional fibroblast populations that reside within the connective tissues of gingiva and periodontal ligament. Notably, after gingival wounding, a fibroblast sub-type (myofibroblast) arises, which is centrally involved in collagen synthesis and fibrillar remodeling. While myofibroblasts are not usually seen in healthy, mature connective tissues, their formation is enhanced by wound-healing cytokines. The formation of myofibroblasts is also modulated by the stiffness of the extracellular matrix, which is mechanosensed by resident precursor cells in the gingival connective tissue microenvironment. Here, we consider the cellular origins and the factors that control the differentiation and matrix remodeling functions of periodontal fibroblasts. An improved understanding of the regulation and function of periodontal fibroblasts will be critical for the development of new therapies to optimize the restoration of periodontal structure and function after wounding.
Highlights
Reviewed by: Natalina Quarto, University of Naples Federico II, Italy Monica Mattioli-Belmonte, Polytechnical University of Marche, Italy
The synthesis and remodeling of nascent collagen matrices are of fundamental importance for the reestablishment of a functional periodontium and are mediated by diverse, multi-functional fibroblast populations that reside within the connective tissues of gingiva and periodontal ligament
The formation of myofibroblasts is modulated by the stiffness of the extracellular matrix, which is mechanosensed by resident precursor cells in the gingival connective tissue microenvironment
Summary
Wound healing comprises a series of sequential phases that are initiated after tissue damage. If pro-inflammatory mediators are continuously elevated, as is seen in periodontitis, idiopathic pulmonary lung disease, and glomerulonephritis, there is often extensive degradation followed by excessive production of disorganized connective tissue matrices The formation of these dense, dysfunctional, highly cross-linked collagen matrices is frequently manifested in fibrotic lesions that affect a large array of organs and tissues, including the periodontium (Coelho and McCulloch, 2016). During early phases of wound healing, a provisional matrix composed primarily of platelets, fibrin, and fibronectin, undergoes progressive, time-dependent alterations of organization, composition, and structure These alterations involve the sequential degradation of the original components of the nascent matrix and their replacement by newly synthesized matrix molecules including collagens, fibronectin and proteoglycans (Rognoni et al, 2018). Later on in this article, we will focus in particular on phase (3), tissue remodeling
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