University of Oulu

Huovinen, J, Lohela, J, Kauppinen, S, et al. No adverse effects on periarticular tissue by intra-articular vitamin D analogue calcipotriol in a reduced-dose zymosan-induced arthritis model in rats. Basic Clin Pharmacol Toxicol. 2023; 132( 2): 131- 143. doi:10.1111/bcpt.13815

No adverse effects on periarticular tissue by intra-articular vitamin D analogue calcipotriol in a reduced-dose zymosan-induced arthritis model in rats

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Author: Huovinen, Jere1; Lohela, Jesse2; Kauppinen, Sami2;
Organizations: 1Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
2Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
3Oulu Laboratory Animal Centre, Oulu University Hospital and University of Oulu, Oulu, Finland
4Division of Rheumatology, Kuopio University Hospital, Kuopio, Finland
5Division of Operative Care, Oulu University Hospital and University of Oulu, Oulu, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe202301203949
Language: English
Published: John Wiley & Sons, 2023
Publish Date: 2024-01-06
Description:

Abstract

Calcipotriol, a vitamin D analogue, is an antiproliferative and anti-inflammatory drug currently used in psoriasis. Here, our aim was to analyse the safety of calcipotriol for cartilage and bone in alleviated-dose (0.1 mg instead of usual ≥1mg dose) zymosan-induced arthritis in rats. Theoretically, high doses of vitamin D or analogues could have detrimental effects on bone or cartilage. The rats were divided into four groups: vehicle (n = 9), dexamethasone 0.1 mg/kg (n = 9), calcipotriol 0.1 mg/kg (n = 8) and negative control (n = 10) with no injections. Arthritic rats were given phosphate-buffered saline (PBS) injections to left knees as a control. After euthanasia on day 8, all knees were imaged with micro-computed tomography for surface lesions and decalcified for histological analyses. Contrary to our expectations, no significant changes could be observed in the tomography data and histological scores among the three treatment groups or between the vehicle-treated and non-arthritic group. Calcipotriol did not cause adverse effects on cartilage or subchondral bone within a week, suggesting that it could be safely used in local treatment of arthritis. The alleviated model caused synovitis with local and systemic inflammatory response without cartilage erosions, which might be useful in studying self-limiting synovitis where cartilage or bone effects are not of primary interest.

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Series: Basic & clinical pharmacology & toxicology
ISSN: 1742-7835
ISSN-E: 1742-7843
ISSN-L: 1742-7835
Volume: 132
Issue: 2
Pages: 131 - 143
DOI: 10.1111/bcpt.13815
OADOI: https://oadoi.org/10.1111/bcpt.13815
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
317 Pharmacy
Subjects:
Funding: The work was funded by Finnish Medical Foundation, Sigrid Juselius Foundation, Northern Ostrobothnia Hospital District and the Finnish Society for Rheumatology. The funders did not have a role in study design, data acquisition and analysis, writing, or decision to publish the manuscript. This work was carried out with the support of The Oulu Laboratory Animal Centre Research Infrastructure, University of Oulu, Finland.
Copyright information: © 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Huovinen, J, Lohela, J, Kauppinen, S, et al. No adverse effects on periarticular tissue by intra-articular vitamin D analogue calcipotriol in a reduced-dose zymosan-induced arthritis model in rats. Basic Clin Pharmacol Toxicol. 2023; 132( 2): 131- 143, which has been published in final form at https://doi.org/10.1111/bcpt.13815. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.