Matrix mechanics and regulation of the fibroblast phenotype

The oral cavity hosts a variety of different fibroblast populations that are generally responsible for maintaining homeostasis of the soft connective tissue. In addition to regulating the turnover and structural arrangement of collagen and other proteins of the extracellular matrix, fibroblasts perform a number of specialized functions. Certain fibroblast subpopulations in the gingiva, oral mucosa and periodontal ligament serve as progenitor cells with multilineage differentiation and self-renewal characteristics. In the periodontal ligament, fibroblasts further appear to function as mechanosensing entities that regulate collagen-secretory and collagen-remodeling activities according to the level of strain in the ligament. Mechanical challenge also plays an important role during the activation of periodontal fibroblasts in response to injury. Dysregulation of this activation process can lead either to poor healing and chronic wounds or to overly healed wounds with fibrosis. This review will elaborate on the roles of mechanical factors and mechanoperception in fibroblast activation, the molecular features of activated fibroblasts and the regulation mechanisms of fibroblast contraction. Pharmacological interference at each level is currently being pursued to improve the outcome of healing of injured periodontal tissue.