Alterations in Anandamide Synthesis and Degradation during Osteoarthritis Progression in an Animal Model.

Aleksandra Pędracka,Marta Bryk,Jakub Mlost,Magdalena Kostrzewa,Jakub Chwastek,Katarzyna Starowicz

doi:10.3390/ijms21197381

Aleksandra Pędracka, Marta Bryk + Show 4 more

Open Access

https://doi.org/10.3390/ijms21197381

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Abstract

Osteoarthritis (OA) is a degenerative joint disease manifested by movement limitations and chronic pain. Endocannabinoid system (ECS) may modulate nociception via cannabinoid and TRPV1 receptors. The purpose of our study was to examine alterations in the spinal and joint endocannabinoid system during pain development in an animal model of OA. Wistar rats received intra-articular injection of 3mg of sodium monoiodoacetate (MIA) into the knee joint. Animals were sacrificed on day 2, 7, 14, 21, 28 after injection and lumbar spinal cord, cartilage and synovium were collected. Changes in the transcription levels of the ECS elements were measured. At the spinal level, gene expression levels of the cannabinoid and TRPV1 receptors as well as enzymes involved in anandamide synthesis and degradation were elevated in the advanced OA phase. In the joint, an important role of the synovium was demonstrated, since cartilage degeneration resulted in attenuation of the changes in the gene expression. Enzymes responsible for anandamide synthesis and degradation were upregulated particularly in the early stages of OA, presumably in response to early local joint inflammation. The presented study provides missing information about the MIA-induced OA model and encourages the development of a therapy focused on the molecular role of ECS.

Highlights

Osteoarthritis (OA) is a whole joint disease characterized by cartilage destruction, subchondral bone alterations and synovial membrane inflammation
Preclinical studies suggest, that endocannabinoids have a potential to become novel molecular targets for drug development in chronic pain, including pain resulting from osteoarthritis [4]
We examined changes in the transcription of the Endocannabinoid system (ECS) system elements, including cannabinoid receptors and multiple AEA synthesis and degradation enzymes, in the lumbar spinal cord, cartilage and synovial membrane of osteoarthritic rats

Summary

Introduction

Osteoarthritis (OA) is a whole joint disease characterized by cartilage destruction, subchondral bone alterations and synovial membrane inflammation. OA is a leading cause of chronic pain and disability worldwide [1]. Current treatment is very limited and is mainly based on symptomatic pain relief by nonsteroidal anti-inflammatory drugs (NSAIDs) offering insufficient pain relief [2,3]. OA remains among the most challenging joint diseases due to the lack of self-healing capacity of articular cartilage and there is no cure for it. An extensive search for new treatment options is needed. Preclinical studies suggest, that endocannabinoids have a potential to become novel molecular targets for drug development in chronic pain, including pain resulting from osteoarthritis [4]

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