University of Oulu

Aleksiuk V, Baleisis J, Kirdaite G, Uzieliene I, Denkovskij J, Bernotas P, Ivaskiene T, Mobasheri A, Bernotiene E. Evaluation of Cartilage Integrity Following Administration of Oral and Intraarticular Nifedipine in a Murine Model of Osteoarthritis. Biomedicines. 2023; 11(9):2443.

Evaluation of cartilage integrity following administration of oral and intraarticular nifedipine in a murine model of osteoarthritis

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Author: Aleksiuk, Viktorija1; Baleisis, Justinas2; Kirdaite, Gailute3;
Organizations: 1Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, 08406 Vilnius, Lithuania
2Department of Biomodels, State Research Institute Centre for Innovative Medicine, 08406 Vilnius, Lithuania
3Department of Experimental, Preventive and Clinical Medicine, State Research Institute Centre for Innovative Medicine, 08406 Vilnius, Lithuania
4Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland
5World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, B-4000 Liège, Belgium
6Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 17.9 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2023
Publish Date: 2023-10-16


Osteoarthritis (OA) ranks as the prevailing type of arthritis on a global scale, for which no effective treatments are currently available. Arterial hypertension is a common comorbidity in OA patients, and antihypertensive drugs, such as nifedipine (NIF), may affect the course of OA progression. The aim of this preclinical study was to determine the effect of nifedipine on healthy and OA cartilage, depending on its route of administration. In this study, we used the destabilization of medial meniscus to develop a mouse model of OA. Nifedipine was applied per os or intraarticularly (i.a.) for 8 weeks to both mice with OA and healthy animals. Serum biomarker concentrations were evaluated using the Luminex platform and alterations in the knee cartilage were graded according to OARSI histological scores and investigated immunohistochemically. Nifedipine treatment per os and i.a. exerted protective effects, as assessed by the OARSI histological scores. However, long-term nifedipine i.a. injections induced the deterioration of healthy cartilage. Lubricin, cartilage intermediate layer matrix protein (CILP), collagen type VI (COLVI), CILP, and Ki67 were upregulated by the nifedipine treatment. Serum biomarkers MMP-3, thrombospondin-4, and leptin were upregulated in the healthy groups treated with nifedipine, while only the levels of MMP-3 were significantly higher in the OA group treated with nifedipine per os compared to the untreated group. In conclusion, this study highlights the differential effects of nifedipine on cartilage integrity, depending on the route of administration and cartilage condition.

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Series: Biomedicines
ISSN: 2227-9059
ISSN-E: 2227-9059
ISSN-L: 2227-9059
Volume: 11
Issue: 9
Article number: 2443
DOI: 10.3390/biomedicines11092443
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was funded by the European Structural and Social Funds through the Research Council of Lithuania (Lietuvos Mokslo Taryba) according to the activity Attracting Foreign Researchers for Research Implementation (2018–2022), Grant No 01.2.2-LMT-K-718-02-0022; High-level R&D project: “L-type calcium channels as potential therapeutic targets for osteoarthritic cartilage metabolic processes” 09.3.3-LMT-K-712-01-0157 (Project number: DOTSUT-215).
Copyright information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (