Modulation of the mechanical responses of synovial fibroblasts by osteoarthritis-associated inflammatory stressors.

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Jamal, Juliana ORCID: 0000-0002-8973-7556, Roebuck, Margaret M ORCID: 0000-0002-1193-5149, Lee, Siam-Yee, Frostick, Simon P, Abbas, Azlina Amir, Merican, Azhar Mahmood, Teo, Seow-Hui, Wood, Amanda, Tan, Sik-Loo, Bou-Gharios, George et al (show 1 more authors) and Wong, Pooi-Fong (2020) Modulation of the mechanical responses of synovial fibroblasts by osteoarthritis-associated inflammatory stressors. The International Journal of Biochemistry and Cell Biology, 126. 105800-.

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Abstract

OBJECTIVES:To compare mechanobiological response of synovial fibroblasts (SFb) from OA patient cohorts under mechanical load and inflammatory stressors for better understanding of SFb homeostatic functions. METHODS:Primary SFb isolated from knee synovium of OA obese (OA-ob:SFb), OA-pre-obese (OA-Pob:SFb), non-OA arthroscopic (scope:SFb), and non-OA arthroscopic with cartilage damage (scope-CD:SFb) were exposed to OA-conditioned media (OACM), derived from OA obese (OA-ob:CM), OA-pre-obese (OA-Pob:CM), and mechanical stretch at either 0 %, 6 % or 10 % for 24 h. Differences in the mRNA levels of genes involved in extracellular matrix production, inflammation and secretory activity were measured. RESULTS:Despite the significant BMI differences between the OA-ob and OA-Pob groups, OA-Pob has more patients with underlying dyslipidaemia, and low-grade synovitis with higher levels of secreted proteins, CXCL8, COL4A1, CCL4, SPARC and FGF2 in OA-Pob:CM. All primary SFb exhibited anti-proliferative activity with both OA-CM. Mechanical stretch stimulated lubricin production in scope:SFb, higher TGFβ1 and COL1A1 expressions in scope-CD:SFb. OA-Pob:CM stimulated greater detrimental effects than the OA-ob:CM, with higher pro-inflammatory cytokines, IL1β, IL6, COX2 and proteases such as aggrecanases, ADAMTS4 and ADAMTS5, and lower ECM matrix, COL1A1 expressions in all SFb. OA-ob:SFb were unresponsive but expressed higher pro-inflammatory cytokines under OA-Pob:CM treatment. CONCLUSION:Both mechanical and inflammatory stressors regulate SFb molecular functions with heterogeneity in responses that are dependent on their pathological tissue of origins. While mechanical stretch promotes a favorable effect with enhanced lubricin production in scope:SFb and TGFβ1 and COL1A1 in scope-CD:SFb, the presence of excessively high OA-associated inflammatory mediators in OA-Pob:CM, predominantly SPARC, CXCL8 and FGF2 drive all SFb regardless of pathology, towards greater pro-inflammatory activities.

Item Type:	Article
Uncontrolled Keywords:	Osteoarthritis, Synovial fibroblasts, Mechanical stress, Inflammatory response, Obesity, Mediators of inflammation
Depositing User:	Symplectic Admin
Date Deposited:	02 Nov 2020 10:06
Last Modified:	18 Jan 2023 23:39
DOI:	10.1016/j.biocel.2020.105800
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3095704