Osteoarthritis is more common in women than men in older age, but researchers have struggled to pinpoint precisely why this is. A new study may have shed light on the issue, after identifying differences in the synovial fluid of men and women with the disease.
Synovial fluid is the fluid that surrounds the joints. It helps to protect cartilage - which is the tissue that covers the ends of the bones - against damaged caused by friction during movement.
Synovial fluid is known to contain information that can be used to determine the health of a joint. For the new study, researchers set out to investigate whether there were differences in this information between men and women with osteoarthritis (OA).
Study co-author Dr. Monte Hunter, chair of the Department of Orthopedic Surgery at the Medical College of Georgia at Augusta University, and colleagues recently published their findings in the journal Scientific Reports.
For the study, the team analyzed samples of synovial fluid taken from the knees of men and women both with and without OA.
The researchers focused on the exosomes of synovial fluid, which are vesicles within the fluid that carry small molecules called microRNAs (miRNAs). These regulate gene expression.
Estrogen has a part to play
The analysis revealed significant differences in miRNA activity between men and women with OA.
Specifically, they found that the synovial fluid of men showed 69 downregulated and 45 upregulated miRNAs, while the the synovial fluid of women had 91 downregulated and 53 upregulated miRNAs.
This microRNA activity was associated with 70 altered biological processes among women, compared with approximately 50 altered biological processes among men.
Interestingly, the researchers found that women were more likely than men to show a deactivation or alteration of miRNAs that are important for estrogen signaling and collagen production.
The team notes that lower estrogen levels - which normally arise as a result of menopause - are associated with a greater production of bone-destroying cells. What is more, studies have linked hormone replacement therapy, which boosts estrogen levels, with a lower risk of OA.
Taking this information into account, the researchers believe that their findings indicate that estrogen influences miRNA levels within the exosomes of synovial fluid.
Further confirming their theory, the researchers found that blocking estrogen availability in exosomes using aromatase inhibitors led to a reduction in miRNAs.
Potential cause of OA uncovered
Additionally, the study may have shed light on a cause of OA in both sexes. The team identified one miRNA, called MiR-504-3p, that was upregulated in both men and women with OA.
While the researchers are unable to explain the exact role of MiR-504-3p in OA, they believe that it may be involved in cartilage degeneration, which is the root cause of the disease.
Based on this finding, Dr. Hunter and colleagues plan to conduct further studies, which will investigate the effects of MiR-504-3p inhibition on OA development.
In the meantime, the researchers believe that their current findings help to explain why women are at greater risk of OA than men.
"To conclude, this is the first study to demonstrate gender-specific miRNA profiling in EVs [extracellular vesicles] of synovial fluid in human OA," write the authors.
"Synovial fluid derived exosomes play an important role in the pathophysiology of OA. Furthermore, these differentially expressed female miRNAs might be estrogen-responsive and play a role in TLR [toll-like receptor] signaling during pathogenesis of OA."