Is Fibroblast Heterogeneity Relevant To the Health, Diseases, and Treatments of Periodontal Tissues?

Abstract

There are wide variations of gene expression and strikingly different responses to extracellular signals among different fibroblast populations. This has prompted a large number of in vitro studies which suggest that fibroblasts are not homogeneous but instead comprise multiple subpopulations with extensive site-to-site and intra-site variations. Conceivably, either fibroblasts are not all created equal, or, alternatively, discrete subpopulations may emerge in development, inflammatory lesions, or wound healing. While the heterogeneous nature of cultured fibroblasts has been known for some time, are these variations relevant to our understanding of the biology of oral tissues, their involvement in disease, and their response to therapy? Since fibroblasts are the predominant cell type in soft connective tissue matrices, the regulation of their proliferative, synthetic, and degradative behavior is likely to be important in tissue physiology and pathology. In this review, we use the current literature to assess whether fibroblast subpopulations really make a difference in the health and disease of periodontal tissues. We address the following questions: (1) Is fibroblast heterogeneity a real in vivo phenomenon? (2) How can we advance our knowledge of phenotypic variations and the regulation of fibroblast differentiation? (3) Could a knowledge of fibroblast heterogeneity have an impact on the development of new approaches to pathogenesis and the treatment of periodontal tissues?

Dynamic role of myofibroblasts in oral lesions

“…Oral mucosa comprises stratified squamous epithelium, and its underlying connective tissue harbours various mesenchymal cells such as fibroblasts, endothelial cells, and pericytes [1,2] . These cells and their extracellular matrix (ECM) play pivotal roles in cell differentiation and proliferation during tissue development, wound healing processes, and pathological alterations [2,3] .…”

Differential effect of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans on co-cultures of human oral cells

“…In conjunction with other resident cell types, these cells are responsible for maintaining the structural integrity of the periodontium, as well as facilitating the repair and/or regeneration of these tissues following injury (Lekic et al, 1997). We recently showed that fibroblasts derived from human periodontal ligament (HPLFs) did not display growth inhibition, cellcycle arrest or dsDNA damage typically associated with CDT (Kanno et al, 2005).…”

Endogenous IL-15 Sustains Recruitment of IL-2Rβ and Common γ and IL-2-Mediated Chemokine Production in Normal and Inflamed Human Gingival Fibroblasts

“…F ibroblasts and their extracellular matrix products play pivotal roles in maintaining the structural integrity of connective tissues, in healing processes, and in pathological alterations (1,2). Fibroblasts are not a homogeneous population in different anatomical regions or even within a single tissue, and are considered to actively define the structure of microenvironments and modulate immune cell behavior by conditioning the local and cellular microenvironment (1,2).…”

“…Fibroblasts are not a homogeneous population in different anatomical regions or even within a single tissue, and are considered to actively define the structure of microenvironments and modulate immune cell behavior by conditioning the local and cellular microenvironment (1,2). Human gingival fibroblasts (HGF), 3 the major constituent of gingival connective tissue, have been shown to express immunologic receptors, such as a bacterial pattern recognition receptor CD14 (3,4), TLRs (5), and costimulatory molecule CD40 (1,6) and to produce various cytokines, such as IL-1, IL-6, IL-8, and MCP-1, by interaction with their ligands (3)(4)(5)7).…”