Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis

Előd Nagy; Enikő Vajda; Camil Vari; Sándor Sipka; Ana-Maria Fárr; Emőke Horváth

doi:10.7717/peerj.3185

Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis

PeerJ. 2017 Apr 12:5:e3185. doi: 10.7717/peerj.3185. eCollection 2017.

Authors

Előd Nagy¹, Enikő Vajda², Camil Vari³, Sándor Sipka⁴, Ana-Maria Fárr⁵, Emőke Horváth⁶

Affiliations

¹ Department of Biochemistry and Environmental Chemistry, University of Medicine and Pharmacy, Targu-Mures, Romania.
² Department of Drug Analysis, University of Medicine and Pharmacy, Targu-Mures, Romania.
³ Department of Pharmacology, University of Medicine and Pharmacy of Targu Mures, Targu-Mures, Romania.
⁴ Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen, Hungary.
⁵ Department of Pathophysiology, University of Medicine and Pharmacy, Targu-Mures, Romania.
⁶ Department of Pathology, University of Medicine and Pharmacy, Targu-Mures, Romania.

Abstract

Objective: This study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle.

Methods: Thirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P, n = 11), low-dose (GrpM Lo, 0.2 mg/kg, n = 12) or high-dose (GrpM Hi, 1 mg/kg, n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11.

Results: Compared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 and p = 0.014) and high-dose (p = 0.003 and p = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed.

Conclusion: In this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.

Keywords: Cox-2; Inflammation; Meloxicam; Mono-iodoacetate; OARSI histopathology initiative; Osteoarthritis; Subchondral bone.

Grants and funding

All the funding of this work was supported by the Sectorial Operational Programme Human Resources Development (SOPHRD), financed by the European Social Fund and by the Romanian Government under the contract number POSDR 80641, and research contract no. 6/30.10.2013 and 0345/26.02.2016 with the Studium-Prospero Foundation. There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.