Khadija M. Alawi
Transient receptor potential canonical 5 (TRPC5) protects against pain and vascular inflammation in arthritis and joint inflammation
Alawi, Khadija M.; Russell, Fiona A.; Aubdool, Aisah A.; Srivastava, Salil; Riffo-Vasquez, Yanira; Baldissera, Lineu; Thakore, Pratish; Saleque, Nurjahan; Fernandes, Elisabeth S.; Walsh, David A.; Brain, Susan D.
Fiona A. Russell
Aisah A. Aubdool
Elisabeth S. Fernandes
David A. Walsh
Susan D. Brain
Objective: Transient receptor potential canonical 5 (TRPC5) is functionally expressed on a range of cells including fibroblast-like synoviocytes, which play an important role in arthritis. A role for TRPC5 in inflammation has not been previously shown in vivo. We investigated the contribution of TRPC5 in arthritis.
Methods: Male wild-type and TRPC5 knockout (KO) mice were used in a complete Freund’s adjuvant (CFA)-induced unilateral arthritis model, assessed over 14 days. Arthritis was determined by measurement of knee joint diameter, hindlimb weightbearing asymmetry and pain behaviour. Separate studies involved chronic pharmacological antagonism of TRPC5 channels. Synovium from human post-mortem control and inflammatory arthritis samples were investigated for TRPC5 gene expression.
Results: At baseline, no differences were observed. CFA-induced arthritis resulted in increased synovitis in TRPC5 KO mice assessed by histology. Additionally, TRPC5 KO mice demonstrated reduced ipsilateral weightbearing and nociceptive thresholds (thermal and mechanical) following CFA-induced arthritis. This was associated with increased mRNA expression of inflammatory mediators in the ipsilateral synovium and increased concentration of cytokines in synovial lavage fluid. Chronic treatment with ML204, a TRPC5 antagonist, augmented weightbearing asymmetry, secondary hyperalgesia and cytokine concentrations in the synovial lavage fluid. Synovia from human inflammatory arthritis demonstrated a reduction in TRPC5 mRNA expression.
Conclusions: Genetic deletion or pharmacological blockade of TRPC5 results in an enhancement in joint inflammation and hyperalgesia. Our results suggest that activation of TRPC5 may be associated with an endogenous anti-inflammatory/analgesic pathway in inflammatory joint conditions.
|Journal Article Type||Article|
|Publication Date||Feb 28, 2017|
|Journal||Annals of the Rheumatic Diseases|
|Publisher||BMJ Publishing Group|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Alawi, K. M., Russell, F. A., Aubdool, A. A., Srivastava, S., Riffo-Vasquez, Y., Baldissera, L., …Brain, S. D. (2017). Transient receptor potential canonical 5 (TRPC5) protects against pain and vascular inflammation in arthritis and joint inflammation. Annals of the Rheumatic Diseases, 76(1), 252-260. https://doi.org/10.1136/annrheumdis-2015-208886|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0|
Alawi et al_transient receptor potential canonical 5.pdf
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
You might also like
Disease Activity Flares and Pain Flares in an early rheumatoid arthritis inception cohort; characteristics, antecedants and sequelae
Presentation / Conference
Self-report central mechanisms trait predicts knee pain persistence in the Knee Pain In the Community (KPIC) cohort
Presentation / Conference