title: Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy.
abstract: Thyroid-associated ophthalmopathy, a process in which the orbital tissues become inflamed and are remodeled, occurs with a variable presentation. In some patients, eye muscle enlargement predominates. In others, the connective/adipose tissue enlargement appears the more significant problem. Orbital fibroblasts exhibit heterogeneous phenotypes in culture. Here we report that fibroblasts derived from the connective/adipose tissue depot are distinct from those investing the extraocular muscles. Connective tissue fibroblasts represent a bimodal population of cells with regard to the surface display of the glycoprotein, Thy-1. Perimysial fibroblasts in contrast express Thy-1 uniformly. In that regard, they resemble those from the skin. When subjected to a newly defined set of culture conditions, adipocyte differentiation occurs in up to 43% of the cells. All adipocytes examined failed to display Thy-1. Fibroblasts derived from perimysium and dermis uniformly do not differentiate into adipocytes when incubated under identical culture conditions. Both Thy-1(+) and Thy-1(-) connective tissue fibroblasts express the adipogenic trigger, peroxisome proliferator activator gamma, suggesting that differences in the potential for differentiation may reside with phenotypic attributes downstream from this receptor/adipogenic transcription factor. These observations enhance our understanding of orbital adipogenesis and define previously unrecognized differences between fibroblasts from the extraocular muscle and connective tissue.
authors.affiliation: Division of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, California 90502, USA. tjsmith@ucla.edu
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Laura
authors.initials: L
authors.lastname: Koumas
authors.forename: AnneMarie
authors.initials: A
authors.lastname: Gagnon
authors.forename: Andrea
authors.initials: A
authors.lastname: Bell
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
authors.forename: Alexander
authors.initials: A
authors.lastname: Sorisky
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006111:Graves Disease / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009915:Orbit / Q000473:pathology*; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000032:analysis / Q000096:biosynthesis; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D018800:Thy-1 Antigens / Q000032:analysis; D014157:Transcription Factors / Q000819:agonists / Q000032:analysis / Q000096:biosynthesis
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D018800:Thy-1 Antigens; D014157:Transcription Factors; D000077154:Rosiglitazone