University of Oulu

Huhtakangas JA, Huovinen J, Laaksonen S, Voipio H-M, Vuolteenaho O, Finnilä MAJ, et al. (2021) A single intra-articular dose of vitamin D analog calcipotriol alleviates synovitis without adverse effects in rats. PLoS ONE 16(4): e0250352.

A single intra-articular dose of vitamin D analog calcipotriol alleviates synovitis without adverse effects in rats

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Author: Huhtakangas, Johanna A.1,2; Huovinen, Jere1; Laaksonen, Sakari3;
Organizations: 1Cancer Research and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
2Department of Medicine, Rheumatology Unit, Oulu University Hospital, Medical Research Center Oulu, Oulu, Finland
3Oulu Laboratory Animal Center, Department of Experimental Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland
4Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
5Faculty of Medicine, Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
6Division of Operative Care, Oulu University Hospital and University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.8 MB)
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Language: English
Published: Public Library of Science, 2021
Publish Date: 2021-06-11


1,25-dihydroxyvitamin-D₃ and its derivatives have shown anti-arthritic and chondroprotective effects in experimental animal models with prophylactic dosing. The purpose of this preliminary study was to test the efficacy and safety of calcipotriol, vitamin D analog, as a treatment for a fully-developed knee arthritis in Zymosan-induced arthritis (ZIA) model. Forty 5-month-old male Sprague-Dawley rats were randomized into three arthritis groups and a non-arthritic control group with no injections (10 rats/group). A day after Zymosan (0.1 mg) had been administrated into the right knee joints, the same knees were injected with calcipotriol (0.1 mg/kg), dexamethasone (0.1 mg/kg) or vehicle in a 100 μl volume. The left control knees were injected with saline (PBS) on two consecutive days. All injections, blood sampling and measurements were performed under general anesthesia on days 0, 1, 3 and 8. Internal organs and knees were harvested on day 8 and the histology of the whole knees was assessed blinded. Joints treated with calcipotriol showed a milder histological synovitis than those treated with vehicle (p = 0.041), but there was no statistically significant difference between the dexamethasone and vehicle groups. The clinical severity of arthritis did not differ between the arthritis groups measured by body temperature, swelling of the knee, thermal imaging, clinical scoring or cytokine levels on days 1, 3 and 8. Weight loss was bigger in rats treated with dexamethasone, propably due to loss of appetite,compared to other arthritis groups on days 2–3 (p<0.05). Study drugs did not influence serum calcium ion and glucose levels. Taken together, this preliminary study shows that a single intra-articular injection of calcipotriol reduces histological grade of synovitis a week after the local injection, but dexamethasone did not differ from the vehicle. Calcipotriol may have an early disease-modifying effect in the rat ZIA model without obvious side effects.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 16
Issue: 4
Article number: e0250352
DOI: 10.1371/journal.pone.0250352
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by -the Finnish Medical Foundation (J.A.H.) -the Finnish Society for Rheumatology- (J.H.).
Copyright information: © 2021 Huhtakangas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.