CRTAC1 as a biomarker for osteoarthritis: Link to inflammation and microRNA regulation

This study aimed to evaluate the profile of CRTAC1, a cartilage-associated protein, in the synovial fluid (SF) and plasma of individuals with osteoarthritis (OA) compared to controls. We assessed CRTAC1's specificity, explored differences among OA subtypes, and examined the link between inflammation, CRTAC1, and miRNAs potentially regulating its expression.

A total of 555 individuals participated, including 68 paired SF and plasma samples from individuals with OA, 51 post-traumatic effusion controls (PT-controls), and 95 healthy controls (HC) for plasma analyses. Knee radiographs were evaluated using the Kellgren-Lawrence grading scale. CRTAC1 levels were measured by mass spectrometry and validated via Immunoquantitative (IQ)-ELISA. Pro-inflammatory 27-plex assays were also validated by IQ-ELISA, and miRNA sequencing was followed by digital PCR validation.

CRTAC1 levels were significantly higher in OA SF (33×) and plasma (32×) compared to controls, with greater concentrations in plasma. CRTAC1 in SF, but not plasma, correlated with OA severity (β=0.5). Associations were also identified between CRTAC1 and eotaxin in SF (β=0.14) and plasma (β=0.09). miR-10a-5p (2.5×), miR-107 (38×), and miR-186-5p (9.3×) were downregulated in controls compared to OA and inversely associated with CRTAC1 in SF.

CRTAC1 has emerged as a potential biomarker for OA, with SF levels associated to disease severity and inflammation. Additionally, the identified miRNAs may play a role in regulating CRTAC1, contributing to OA progression. Although further research is needed to understand the mechanism of CRTAC1 in OA and its therapeutic prospects, our results indicate its potential as a biomarker of OA severity.