Independent Adipogenic and Contractile Properties of Fibroblasts in Graves’ Orbitopathy: An In Vitro Model for the Evaluation of Treatments

• DOI: 10.1371/journal.pone.0095586
• Publication Date: 2014-04-21T20:42:21Z
• Authors: He Li; Caroline Fitchett; Katarzyna Kozdon; Hari Jayaram; Geoffrey E. Rose; Maryse Bailly; Daniel G. Ezra
• Keywords: Male; 0301 basic medicine; Adipogenesis; Science; Q; R; Fibroblasts; Middle Aged; Models, Biological; Extracellular Matrix; Graves Ophthalmopathy; 03 medical and health sciences; Phenotype; Pressure; Medicine; Humans; Thy-1 Antigens; Female; Cells, Cultured; Research Article; Aged

Graves' orbitopathy (GO) is a disfiguring and sometimes blinding disease, characterised by inflammation swelling of orbital tissues, with fibrosis adipogenesis being predominant features. Little known about the disease aetiology molecular mechanisms driving phenotypic changes in fibroblasts are unknown. Using isolated from fat undiseased individuals or GO patients, we have established novel vitro model to evaluate dual profile cells three-dimensional collagen matrix; this pseudo-physiological 3D environment allows measurement their contractile adipogenic properties. contracted matrices more efficiently than control following serum TGFβ1 stimulation, showed slightly increased ability proliferate matrix, accordance fibro-proliferative phenotype. cells, unlike controls, also spontaneously differentiated into adipocytes cultures - confirming an intrinsic profile. However, both underwent when cultured under pathological pressure levels. We further demonstrate that Thy-1-low population underlies but not phenotype and, using inhibitors, confirm phenotypes regulated separate pathways. In view current lack suitable treatment for GO, propose new testing duality could be useful as preclinical evaluation efficacy potential treatments.