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Synovial fluid exosomal miRNA content remains altered in OA patients and these gender specific changes plays an integral role in pathophysiology of OA.
Osteoarthritis (OA) is one of the most chronic conditions of joints leading to pain and disability. This disease affects more than 3 million Americans. It causes severe inflammation, pain and restricted movement and severe osteoarthritis may require a knee replacement surgery.
According to a research by Dr Monte Hunter and colleagues published in the journal Scientific Reports, males and females respond differently to OA. This may be attributed to the findings involving the synovial fluid in the joints. Researchers found the difference between the messages sent and received via mRNA. Therefore, scientists looked for what messenger cells in the affected region were sending and receiving the signals. The probe was done by studying the inner travelling compartments in the fluid, known as exosomes. They found an altered number of mRNA in both the patient groups. However, no difference was seen in the number of exosomes. The study was performed by isolating round exosomes in discarded human synovial fluid from persons with and without OA. Among men, 69 downregulated and 45 upregulated mRNAs were found. While in women, 91 downregulated versus 53 upregulated mRNAs were found. From the overall study, women looked more affected. Therefore, this difference can be helpful in explaining difference in disease incidences among men and women. However, one more factor, estrogen, a female hormone was found as a key to the differences. This can be explained by the finding that mRNA that sends messages for the better joint health such as collagen-producing cells and estrogen signaling gets altered or turned off, especially in women. The lower estrogen levels in women enhance cell production that destroys bone, and in environ, these bone-consuming cells live longer and result in a more significant bone loss.
According to scientists, these levels of estrogen play an essential role in figuring out which mRNAs found in exosomes. When healthy female's cartilages cells treated with OA patient’s exosomes, lower number of healthy exosomes were noticed. During this exposure, the gene expression which makes extracellular matrix go down, promotes inflammation get increased. Scientists found mRNA (MiR-504-3p) as a responsible factor for OA in both males and females. Although the underlying mechanism is unclear, scientists believe that this mRNA degenerates cartilages causing OA.
Researchers believe that very soon they will succeed to evaluate exosomes in the fluid for indicators of that patient's specific instigators of cartilage destruction. This will help plan a cocktail – a mix of microRNA inhibitors and joint health promoting microRNA mimics that can be delivered in human-made exosomes to stop the destruction. The researchers are presently analyzing the way to block the microRNAs causing the joint damage.
Medical College of Georgia at Augusta University
Fluid in the knee holds clues for why osteoarthritis is more common in females
Phil Jones
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