Melatonin in regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis: involvement of circadian clock genes

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most prevalent joint diseases. A such, they are important causes of
pain and disability in a substantial proportion of the human population. A common characteristic of these diseases is the erosion of
articular cartilage and consequently joint dysfunction. Melatonin has been proposed as a link between circadian rhythms and
joint diseases including RA and OA. This hormone exerts a diversity of regulatory actions through binding to specific receptors and
intracellular targets as well as having receptor-independent actions as a free radical scavenger. Cytoprotective effects of melatonin
involve a myriad of prominent receptor-mediated pathways/molecules associated with inflammation, of which the role of
omnipresent NF-κB signalling is crucial. Likewise, disturbance of circadian timekeeping is closely involved in the aetiology of
inflammatory arthritis. Melatonin is shown to stimulate cartilage destruction/regeneration through direct/indirect modulation of
the expression of the main circadian clock genes, such as BMAL, CRY and/or DEC2. In the current article, we review the effects of
melatonin on RA and OA, focusing on its ability to regulate inflammatory pathways and circadian rhythms. We also review the
possible protective effects of melatonin on RA and OA pathogenesis.
LINKED ARTICLES
This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic
Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc