Wnt signalling inhibits adipogenesis in orbital fibroblasts from patients with Graves’ orbitopathy

• Published in: British journal of ophthalmology Vol. 106; no. 7; pp. 1019 - 1027
• Main Authors: Jung, Sang Joon, Choi, Yeon Jeong, Park, Tae Kwann, Woo, Sang Earn, Kim, Bo-Yeon, Yoon, Jin Sook, Jang, Sun Young
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01.07.2022; BMJ Publishing Group LTD
• Subjects: Adipocytes; Cell culture; Edema; experimental and laboratory; Fibroblasts; Gene expression; Laboratory science; orbit; Pathogenesis; Proteins; Thyroid gland; United Kingdom > UK; United States > US; California
• ISSN: 0007-1161; 1468-2079; 1468-2079
• DOI: 10.1136/bjophthalmol-2020-316898

Background/AimsTo investigate the role of Wnt signalling in adipogenesis using an in vitro model of Graves’ orbitopathy (GO).MethodsOrbital fat was obtained from patients with GO and non-GO participants for primary orbital fibroblast (OF) culture. Expression levels of Wnt5a, Wnt10b, β-catenin, phospho-β-catenin and cyclin D1 were compared between GO and non-GO OFs. These expression levels were also determined during adipogenesis of GO and non-GO OFs. The effects of a stimulator and inhibitor of Wnt signalling on adipogenesis of GO and non-GO OFs were investigated.ResultsWestern blotting analysis showed significant reductions in β-catenin and cyclin D1 and significant enhancement of phospho-β-catenin in OFs from patients with GO, compared with OFs from non-GO participants (p<0.05). Expression of Wnt5a, Wnt10b, β-catenin and cyclin D1 in OFs was highest on day 0, and then gradually declined after induction of adipogenic differentiation. The expression levels of PPARγ, C/EBPα and C/EBPβ were reduced in Wnt stimulator-treated OFs in a dose-dependent manner. Oil red O staining confirmed that a stimulator of Wnt inhibited adipogenesis in GO OFs.ConclusionThese results indicate that Wnt signalling inhibits adipogenesis in OFs from patients with GO and non-GO participants. Further studies are required to examine the potential of Wnt signalling as a target for therapeutic strategies.