Fibroblast heterogeneity in the periodontium and other tissues

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Abstract
Fibroblasts are the major resident cells which inhabit the periodontal tissues. As such, they are crucial for maintaining the connective tissues which support and anchor the tooth. Little is known of their origins, synthesis of regulatory cytokines and growth factors in health and disease, and importance in soft tissue regeneration. An emerging concept is that fibroblasts are not homogeneous, but instead consist of subsets of cells which can regulate bone marrow-derived cells such as T lymphocytes. Fibroblasts can be separated into subsets on the basis of morphology, size and expression of intermediate filaments as well as collagen subtypes. Differential surface marker expression has also been a key feature to distinguish fibroblast subsets from many tissues. Antigens such as Thy-1, class II MHC, and C1q are among those surface proteins which have been employed successfully to separate fibroblasts. Importantly, these fibroblast subsets are not only antigenically diverse, but also possess distinct functions. Thy 1+ pulmonary fibroblasts can display class II MHC antigens, synthesize IL-1 and can activate T lymphocytes, whereas the Thy 1+ subset is devoid of these functions. Recently, fibroblasts from the human orbit have also been shown to be separable on the basis of Thy 1 surface marker expression. Fibroblasts derived from human gingiva and periodontal ligament also appear to be composed of subsets with a heritable pattern of surface markers which will permit their separation into functional subpopulations. This paper will review findings of fibroblast heterogeneity in periodontal and other tissues. Evidence will be presented for the use of surface markers to delineate functional subsets. The ability to discriminate subsets of fibroblasts will aid in studies of periodontal disease pathogenesis and wound healing.