Origins and functions of cells essential for periodontal repair: the role of fibroblasts in tissue homeostasis

Abstract

A review is undertaken of rodent model systems and cell culture studies that address the role of periodontal fibroblasts in tissue homeostasis in both normal function and after wound healing. Fibroblasts are the predominant cells of the periodontal ligament (PL) and of healthy gingiva and have important roles in the development, function and regeneration of the tooth support apparatus. In normally functioning periodontal tissues cell turnover involves generation of new cells by proliferation which in turn is balanced by apoptopic cell death. Consequently PL fibroblasts comprise a renewal cell system in steady-state. PL cell progenitors can generate multiple types of more differentiated, specialized cells including large numbers of fibroblastic cells and more limited numbers of osteogenic or cementogenic cells. However PL fibroblasts constitutively block osteogenesis and thereby maintain the PL width. Proliferating progenitor cell populations of the PL are enriched in locations adjacent to blood vessels and in contiguous endosteal spaces from where they migrate to the body of the PL. Large increases of cell formation and cell differentiation occur after wounding but surprisingly, the cells that repopulate the PL adjacent to the root surface are largely post-mitotic. As PL cell populations comprise multiple lineages, it is likely that after wounding, the separate phenotypes repopulating the wound site will be selected by environmental factors. Further, the specific repopulating lineages will strongly influence the form and function of the nascent tissue. To illustrate the specificity of fibroblast functions, examples of migratory and contractile fibroblast phenotypes are provided which exhibit constitutively different levels of gelsolin and alpha-smooth muscle actin respectively, cytoskeletal proteins which are markers for these cell types. Fibroblasts contribute to PL homeostasis by their abilities to remodel tissues, to repopulate wounds, to influence the metabolism of other cell types and to create a new fibrous attachment.