Active synthesis of type I collagen homotrimer in Dupuytren’s fibrosis is unaffected by anti-TNF-α treatment

Williamson, Kate, Lee, Katie, Beamish, Emma ORCID: 0000-0002-7000-7641, Carter, Alan ORCID: 0000-0002-7000-7641, Gumbs, Jade ORCID: 0000-0002-3962-4895, Cooper, Gabriella, Cheung, Graham, Brown, Daniel ORCID: 0000-0002-0398-7053, Pettitt, Rob ORCID: 0000-0001-8710-5830, Comerford, Eithne ORCID: 0000-0002-5244-6042
et al (show 2 more authors) (2020) Active synthesis of type I collagen homotrimer in Dupuytren’s fibrosis is unaffected by anti-TNF-α treatment. 2020.07.13.195107-.

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Dupuytren’s disease is a common fibroproliferative disease of the palmar fascia of the hand with advanced cases treated surgically. Anti-tumour necrosis factor (TNF) injection has undergone phase 2 trials and may be effective in slowing early-stage disease progression. Here we sought to determine how new synthesis of type I collagen in Dupuytren’s differs from normal palmar fascia samples and to analyse the role of TNF in aberrant collagen synthesis. Model non-fibrotic, but fibrous connective tissues, were used to analyse active type I collagen protein synthesis in development, ageing and degenerative disease, where it was restricted to early development and ruptured tissue. Dupuytren’s tissue was shown to actively synthesise type I collagen, including abnormal type I collagen homotrimer. TNF-α reduced COL1A2 gene expression only in the presence of serum in 2D cell culture and had opposing effects on collagen protein production in the presence or absence of serum. TNF-α had only limited effects in 3D tendon-like constructs. Anti-TNF did not reduce type I collagen synthesis in 3D tendon-like constructs or prevent type I collagen homotrimer synthesis in Dupuytren’s tissue. Hence, modulation of the TNF-α pathway in Dupuytren’s disease is unlikely to prevent the pathological collagen accumulation that is characteristic of fibrosis.

Item Type: Article
Uncontrolled Keywords: 2 Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal
Depositing User: Symplectic Admin
Date Deposited: 09 Sep 2020 08:18
Last Modified: 25 Apr 2024 21:22
DOI: 10.1101/2020.07.13.195107
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