Inhibition of TGFβ signaling decreases osteogenic differentiation of fibrodysplasia ossificans progressiva fibroblasts in a novel in vitro model of the disease

Bone
Dimitra MichaNathalie Bravenboer

Abstract

Fibrodysplasia ossificans progressiva is a rare genetic disorder characterized by progressive heterotopic ossification. FOP patients develop soft tissue lumps as a result of inflammation-induced flare-ups which leads to the irreversible replacement of skeletal muscle tissue with bone tissue. Classical FOP patients possess a mutation (c.617G>A; R206H) in the ACVR1-encoding gene which leads to dysregulated BMP signaling. Nonetheless, not all FOP patients with this mutation exhibit equal severity in symptom presentation or disease progression which indicates a strong contribution by environmental factors. Given the pro-inflammatory role of TGFβ, we studied the role of TGFβ in the progression of osteogenic differentiation in primary dermal fibroblasts from five classical FOP patients based on a novel method of platelet lysate-based osteogenic transdifferentiation. During the course of transdifferentiation the osteogenic properties of the cells were evaluated by the mRNA expression of Sp7/Osterix, Runx2, Alp, OC and the presence of mineralization. During transdifferentiation the expression of osteoblast markers Runx2 (p<0.05) and Alp were higher in patient cells compared to healthy controls. All cell lines exhibited increase in mine...Continue Reading

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Citations

Sep 11, 2016·Materials Science & Engineering. C, Materials for Biological Applications·T T LiaoN Huang
Dec 21, 2017·Intractable & Rare Diseases Research·Zijuan QiJinxiang Han
Dec 18, 2018·Journal of Cellular Biochemistry·Yuan WangJian-Gang Shi
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Mar 27, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Alejandro VallejosFelipe Simon
Aug 28, 2020·Frontiers in Endocrinology·Elisabeth M W EekhoffMarco N Helder
Jul 9, 2020·Frontiers in Endocrinology·Lauria ClaeysDimitra Micha
Mar 7, 2021·Biomedicines·Francesc VenturaGonzalo Sanchez-Duffhues
Jul 27, 2021·Experimental and Therapeutic Medicine·Zhen HanMeng Li

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