A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage.

Nevzat Selim Gokay,Ahu Senem Demiroz,Banu Vural Gokay,Baran Komur,Alper Gokce,Ibrahim Yilmaz,Sergülen Dervisoglu

doi:10.1155/2016/7857345

Abstract

The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg), inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg), or nitric oxide precursor L-arginine (200 mg/kg). After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P = 0.044) positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

Highlights

Osteoarthritis (OA) is a progressive disorder that involves cartilage loss
As mentioned in methods section, both knees were resected without any defects on Day 1 of the experiment in Group 1, intra-articular SF (15 mg/kg/day) was applied to the defect-induced right knees for 7 days in Group 2, intraarticular SF (15 mg/kg/day) + 7-nitroindazole (50 mg/kg/day) was applied to the defect-induced right knees for 7 days in Group 3, intra-articular SF (15 mg/kg/day) + aminoguanidine (30 mg/kg/day) was applied to the defect-induced right knees for 7 days in Group 4, and intra-articular SF (15 mg/kg/day) + L-arginine (200 mg/kg/day) was applied to the defect-induced right knees for 7 days in Group 5 (Table S1)
Our study demonstrated that the suppression of nitric oxide (NO) synthesis by inducible NOS (iNOS) in rats with an experimental cartilage defect did not affect cartilage regeneration

Summary

Introduction

Osteoarthritis (OA) is a progressive disorder that involves cartilage loss. The search continues for a medical or surgical treatment for the cartilage damage that is often blamed for triggering the disorder. Cartilage loss and subchondral bone resorption are known to develop as a result of a catabolic chemical cascade [1]. Cartilage tissue loss and OA are a result of a breakdown in the balance between cartilage extracellular matrix synthesis and degradation in the catabolic direction [2]. Cytokines that stimulate matrix proteinases (MMP) contribute to the catabolic process [3]. These cytokines trigger the formation of nitric oxide (NO) in the joints [4]. It has been reported that NO causes cartilage degradation by increasing

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Discussion

Conclusion