Evaluation of Cartilage Integrity following Administration of Oral and Intraarticular Nifedipine in a Murine Model of Osteoarthritis

Abstract

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.

A Cross-Sectional Study of Factors Predicting the Duration of the Efficacy of Viscosupplementation in Knee Osteoarthritis

“…We did not record the medication taken by the patients, but in terms of frequency, the most frequently prescribed medications in France are angiotensin II receptor blockers and diuretics followed by beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors [30]. Several experimental studies [31][32][33][34][35][36][37][38][39][40] have shown that certain antihypertensives have potentially beneficial effects on OA, whether through anti-inflammatory, antioxidant, analgesic, or even antidegenerative effects. Our work is therefore in line with the literature on the potential chondroprotective effect of certain antihypertensive medications, but as we did not record the medications, we cannot draw any conclusions in this respect.…”