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Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes

Hansson, Eva and Skiöldebrand, Eva (2021). Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes. Current Research in Pharmacology and Drug Discovery. 2 , 100066
[Research article]

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Abstract

Aims
To treat osteoarthritic chondrocytes and thereby reduce the inflammation with a drug combination that primarily affects 5-HT- and ATP-evoked Ca2+ signaling. In osteoarthritic chondrocytes, Ca2+ signaling is elevated, resulting in increased production of ATP and inflammatory mediators. The expression of TLR4 and Na+/K+-ATPase was used to evaluate the inflammatory status of the cells.
Main methods
Equine chondrocytes were collected from joints with mild structural osteoarthritic changes and cultured in monolayers. The cells were treated with a combination of bupivacaine (1 pM) and sildenafil (1 μM) in combination with vitamin D3 (100 nM). A high-throughput screening system, the Flexstation 3 microplate reader, was used to measure intra- and extracellular Ca2+ signaling after exposure to 5-HT, glutamate, or ATP. Expression of inflammatory receptors was assessed by Western blotting.
Key findings
Drug treatment substantially reduced 5-HT- and ATP-evoked intracellular Ca2+ release and TLR4 expression compared to those in untreated chondrocytes. The combination of sildenafil, vitamin D3 together with metformin, as the ability to take up glucose is limited, increased Na+/K+-ATPase expression.
Significance
The combination of these three therapeutic substances at concentrations much lower than usually used, reduced expression of the inflammatory receptor TLR4 and increased the cell membrane enzyme Na+/K+-ATPase, which regulates cell volume and reduces increased intracellular Ca2+ concentrations. These remarkable results indicate that this drug combination has disease-modifying osteoarthritis drug (DMOAD) properties and may be a new clinical therapy for osteoarthritis (OA).

Authors/Creators:Hansson, Eva and Skiöldebrand, Eva
Title:Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes
Series Name/Journal:Current Research in Pharmacology and Drug Discovery
Year of publishing :2021
Volume:2
Article number:100066
Number of Pages:8
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Accepted version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Pharmacology and Toxicology
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Pathobiology
URN:NBN:urn:nbn:se:slu:epsilon-p-114610
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-114610
Additional ID:
Type of IDID
DOI10.1016/j.crphar.2021.100066
ID Code:26637
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:28 Dec 2021 11:25
Metadata Last Modified:28 Dec 2021 11:31

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