Potential emerging roles of the novel adipokines adipolin/CTRP12 and meteorin-like/METRNL in obesity-osteoarthritis interplay

Background: Several insights into obesity-osteoarthritis (OA) relationship have been recently highlighted. Adipolin and metrnl are new adipokines also secreted by chondrocytes. However, their role in OA, and obesity-OA interplay hasn't been elucidated. Therefore, this study was designed to investigate the circulating as well as synovial fluid (SF) levels of adipolin and metrnl in osteoarthritic-patients compared to non-osteoarthritic subjects, and to study their association with OA-severity, dyslipidemia and insulin resistance (IR). Methods: Patients with osteoarthritis and obesity (n = 30), and subjects with obesity not suffering OA (n = 25) were enrolled in the current study. Circulating and SF-levels of adipolin, metrnl, and insulin, as well as SF-levels of matrix-metalloproteinase-13 (MMP-13) were measured by ELISA. Knee-radiographs using X-ray were done to determine OA-severity, and investigate its association with adipokines' levels. Results: Serum and SF-adipolin levels showed tendency to be lower in OA-patients compared to non-OA-subjects; serum: 0.64 [0.45-0.85] and 0.73 [0.62-0.78] ng/ml, p = 0.174, and SF: 0.53 [0.34-0.69] and 0.63 [0.44-0.74] ng/ml, p = 0.353, respectively. Additionally, serum adipolin showed negative-association with SF-MMP-13. However, when stratifying OA-patients into various severity grades, serum adipolin levels did not show a significant difference between them. Regarding serum metrnl, it was significantly lower in OA-patients compared to non-OA-subjects; 19.68 [10.40-53.40] and 48.83 [20.80-86.60] pg/ml, respectively, p = 0.018. Surprisingly, SFmetrnl levels were higher in OA-patients compared to non-OA-subjects; 912 [367-1524] and 315 [125-484] pg/ ml, respectively, p = 0.007. SF-metrnl showed positive-association with insulin resistance, and negative association with SF-MMP-13. Moreover, higher serum metrnl levels were found to be slightly associated with lower likelihood of OA in subjects with obesity; OR = 0.978, CI (0.960- 0.996), p = 0.02, and its levels were also found to be relatively lower in grade-4 compared to the less severe OA grades. Conclusions: Metrnl, and to a lesser extent adipolin seem to be interrelated with OA. Different in-context regulatory mechanisms for metrnl production from various tissues are strongly suggested. Importantly, the findings of the current study shed lights on metrnl as a potential novel mediator and therapeutic target to consider in obesity-OA interplay.

Automated summary

The study investigated the levels of adipolin and metrnl in osteoarthritic patients and their association with disease severity, dyslipidemia, and insulin resistance. Adipolin levels showed a tendency to be lower in OA patients, while metrnl levels were significantly lower in OA patients. Surprisingly, metrnl levels in synovial fluid were higher in OA patients, indicating a complex relationship between these adipokines and OA.