Miss Nichola Foster^1,3, Dr Lucy Barrett^3,4, Dr Mark Fear³, Dr Andrew Stevenson³, A/Prof Nathan Pavlos⁵, A/Prof Dale Edgar^2,3, W/Prof Fiona Wood^3,6, Dr Edward Raby^3,6, Dr Frank Li⁷, Dr Jason Brown⁸, A/Prof Leila Cuttle⁹, Aleksandra Edmundson⁸

¹School of Physiotherapy, The University Of Notre Dame, Fremantle, Fremantle, Perth, Australia, ²Burn Injury Research Node, Institute for Health Research, The University of Notre Dame , Fremantle, Perth , Australia, ³Burn Injury Research Unit and Fiona Wood Foundation, University of Western Australia, Nedlands, Perth, Australia, ⁴Telethon Kids Institute, Nedlands, Perth, Australia, ⁵School of Biomedical Sciences, University of Western Australia, Nedlands, Perth, Australia, ⁶State Adult Burns Unit, Fiona Stanley Hospital, Murdoch, Perth, Australia, ⁷Physiotherapy Department, Concord Repatriation General Hospital , Sydney, Australia, ⁸Professor Stuart Pegg Adult Burns Centre, Royal Brisbane and Women’s Hospital, Brisbane, Australia, ⁹Queensland University of Technology (QUT), at Centre for Children’s Health Research , South Brisbane, Australia

Abstract:

Heterotopic Ossification (HO) is a debilitating complication of burn and trauma however, the pathophysiology remains unclear and treatment is limited. In heart disease, fibroblasts undergo differentiation towards an osteogenic phenotype and drive calcification of heart muscle (Hortells et al. 2018). This study aimed to: 1) determine whether patients with HO (HO+) have a dermal fibroblast phenotype that is more susceptible to osteogenic differentiation compared to fibroblasts from burn patients without HO (HO-) and 2) identify the key genes and signalling pathways that are different in fibroblasts from HO+ patients compared to HO- patients.

Fibroblasts from skin biopsies, collected from 9 HO+ and 4 HO- subjects, were cultured for RNA extraction. RNA-sequencing and analysis was performed to compare the gene expression profiles of fibroblasts between HO+ and HO- subjects. To confirm the RNAseq data, differentially expressed genes (DEGs) were selected and tested using functional studies. Osteogenic differentiation assays were conducted using fibroblasts from HO+, HO- and uninjured humans, with calcium deposition quantified.

A total of 136 significant DEGs were identified between HO+ and HO- subjects, of which 29 were upregulated, and 107 genes downregulated. Gene Ontology and pathway analysis revealed that upregulated genes were significantly enriched in biological processes including the Wnt signalling pathway and pathways of neurodegeneration respectively. Preliminary data from osteogenic differentiation assays indicates that fibroblasts from HO+ patients exhibit more mineralisation compared to controls.

HO+ fibroblasts appear different in their transcriptome and functional analysis suggests they are more susceptible to osteogenic differentiation, compared to controls. Further validation of these gene targets is ongoing.

1. Hortells, L, Sur S, & Hilaire, C 2018, ‘Cell Phenotype Transitions in Cardiovascular Calcification’, Front. Cardiovasc. Med, Vol 5, no. 27.

Biography:

Nichola is a neurological physiotherapist and is undertaking a PhD through the School of Physiotherapy at The University of Notre Dame, Australia. Her research is investigating the prevalence, risk factors, prevention and treatment of traumatic heterotopic ossification after burn and other trauma / burn, neurological and orthopaedic trauma.