For the first time, researchers have directly implicated serotonin in the paraphysiology of rheumatoid arthritis. Serotonin is mostly known as a neurotransmitter, but this shows that it has other important functions.
In a study published in The American Journal of Pathology, the researchers showed that inducing serotonin deficiency in mice with rheumatoid arthritis led to a decline in the condition of the mouse model. When serotonin or compounds that activate receptors for the neurotransmitter were present, some effects of rheumatoid arthritis were reduced.
"Our study highlights that [serotonin] has a direct immunoregulatory role in arthritis ... and [can] open new perspectives to improve the therapeutic options for patients," said Marie-Christine de Vernejoul, the study's co-lead investigator.
Called collagen-induced arthritis (CIA), the mouse model the researchers used resulted in features similar to what people with rheumatoid arthritis develop, like bone and cartilage destruction and osteoclast activation. Osteoclasts are cells responsible for bone resorption.
The researchers compared CIA effects in normal mice and those that have been bred to be genetically-deficient in tryptophan hydroxylase-1, a crucial enzyme needed for producing serotonin in peripheral tissues.
According to their findings, the researchers saw that osteoclasts were both higher in number and more active in serotonin-deficient mice with arthritis. Additionally, higher levels of bone resorption was reported at both remote sites and affected joints.
Arthritic mice deficient in serotonin also exhibited changes in cytokines, cell-signaling molecules, in their paws. They particularly showed a shift in the balance between Th17 lymphocytes and T cell subtypes.
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When the researchers carried out subsequent experiments using cell cultures, they saw that the balance between Th17 lymphocytes and regulatory T cells normalized when serotonin or compounds that activate receptors for the neurotransmitter were introduced. This points to a direct connection between serotonin and rheumatoid arthritis.
Arthritis is the top cause of disability in the United States. Over 50 million adults have been diagnosed with the condition, while nearly 300,000 babies and children have arthritis or a rheumatic condition. It is estimated that, by 2030, that there will be 67 million Americans diagnosed with arthritis. Rheumatoid arthritis is more common in women than in men.
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