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Pain-Associated Transcriptome Changes in Synovium of Knee Osteoarthritis Patients


Bratus-Neuenschwander, Anna; Castro-Giner, Francesc; Frank-Bertoncelj, Mojca; Aluri, Sirisha; Fucentese, Sandro F; Schlapbach, Ralph; Sprott, Haiko (2018). Pain-Associated Transcriptome Changes in Synovium of Knee Osteoarthritis Patients. Genes, 9(7):E338.

Abstract

Joint pain causes significant morbidity in osteoarthritis (OA). The aetiology of joint pain in OA is not well understood. The synovial membrane as an innervated joint structure represents a potential source of peripheral pain in OA. Here we analyse, using a hypothesis-free next generation RNA sequencing, the differences in protein-coding and non-coding transcriptomes in knee synovial tissues from OA patients with high knee pain ( = 5) compared with OA patients with low knee pain ( = 5), as evaluated by visual analogue scale (VAS). We conduct Gene Ontology and pathway analyses on differentially expressed mRNA genes. We identify new protein-coding, long non-coding RNA and microRNA candidates that can be associated with OA joint pain. Top enriched genes in painful OA knees encode neuronal proteins that are known to promote neuronal survival under cellular stress or participate in calcium-dependent synaptic exocytosis and modulation of GABA(γ-aminobutyric acid)ergic activity. Our study uncovers transcriptome changes associated with pain in synovial microenvironment of OA knees. This sets a firm ground for future mechanistic studies and drug discovery to alleviate joint pain in OA.

Abstract

Joint pain causes significant morbidity in osteoarthritis (OA). The aetiology of joint pain in OA is not well understood. The synovial membrane as an innervated joint structure represents a potential source of peripheral pain in OA. Here we analyse, using a hypothesis-free next generation RNA sequencing, the differences in protein-coding and non-coding transcriptomes in knee synovial tissues from OA patients with high knee pain ( = 5) compared with OA patients with low knee pain ( = 5), as evaluated by visual analogue scale (VAS). We conduct Gene Ontology and pathway analyses on differentially expressed mRNA genes. We identify new protein-coding, long non-coding RNA and microRNA candidates that can be associated with OA joint pain. Top enriched genes in painful OA knees encode neuronal proteins that are known to promote neuronal survival under cellular stress or participate in calcium-dependent synaptic exocytosis and modulation of GABA(γ-aminobutyric acid)ergic activity. Our study uncovers transcriptome changes associated with pain in synovial microenvironment of OA knees. This sets a firm ground for future mechanistic studies and drug discovery to alleviate joint pain in OA.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:4 July 2018
Deposited On:18 Sep 2018 14:50
Last Modified:01 Oct 2018 00:00
Publisher:MDPI Publishing
ISSN:2073-4425
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/genes9070338
PubMed ID:29973527

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