SEX-DEPENDENT RESPONSE OF SERUM CARTILAGE BIOMARKERS TO 5 DAYS DRY IMMERSION

Purpose: Periods of immobilization may lead to cartilage degeneration by triggering catabolic processes. While the effect of unloading on cartilage metabolism in males has been studied, data for females are still lacking. During dry immersion (DI), study participants experience movement restriction (in particular of the lower extremities) in a support-free environment, which allows to investigate the role of immobilization for joint health. Biomarkers of cartilage metabolism are responsive to alterations in both biological and mechanical environments, serving as an early indicator of changes in cartilage homeostasis. The purpose of our study was to investigate the effect of 5 days of DI on several serum cartilage biomarkers in female and male volunteers.
Methods: The study was carried out at the Institute de Médecine et de Physiologie Spatiales (MEDES) in Toulouse, France. Eighteen healthy female participants (29±5 years, 165±6 cm, 59±6 kg) and nineteen male participants (28±4 years, 177±4 cm, 72±7 kg) were subjected to four days of baseline data collection (BDC), five days of DI (24hrs/day), and three days of recovery (R). Fasting, venous blood samples were taken at five time points at 7 am: BDC-50h, BDC-26h, DI46h, DI118h and R+46h. We analyzed serum (s) concentrations of COMP (BioVendor R&D®, Brno Czech Republic), C2C and CPII (IBEX Pharmaceuticals Inc., Montreal, Québec, Canada) with commercially available ELISAs. sColl2-1 was analyzed by Artialis SA, Liège, Belgium. All parameters were tested for normal distribution (Kolmogorov-Smirnov test). Not normal distributed parameters were transformed (inverse transformation) for further analysis. Subsequently, repeated measures ANOVA (LSD post-hoc test) with sex as between-subjects factor was carried out.

Results: In Table 1 relative values (normalized to 100% BDC-50h) for all biomarkers are presented. sCOMP levels did not differ between females and males (p=0.831). As a result, data from both sexes were pooled for further analysis. During BDC, sCOMP level were stable (BDC-26h vs. BDC-50h, p=0.321) and then decreased substantially during DI (DI46h vs. BDC-26h, p<0.001). sCOMP levels remained lower (DI118h vs. DI46h, p=0.071) and increased after remobilization (R+46h vs. DI118h, p<0.001). sCPII concentrations were not different between sexes (p=0.942) and were pooled for further analysis. During BDC sCPII levels decreased (BDC-26h vs. BDC-50h, p=0.014) and increased in course of DI (DI46h vs. BDC-26h, p=0.004; DI118h vs. DI46h, p=0.005). During R, sCPII level remained increased (R+46h vs. DI118h, p=0.986). sC2C levels were higher in males compared to females (p=0.008), but the response to DI was similar. During BDC sC2C stayed constant (BDC-26h vs. BDC-50h, males: p=0.238, females: p=0.241) and then increased in both groups during immobilization (DI46h vs. BDC-26h, males: p=0.003, females: p=0.017; DI118h vs. DI46h, males: p=0.039, females: p=0.022). After remobilization, sC2C for females remained increased (R+46h vs. DI118h, p=0.784), while for the males a reduction could be detected (R+46h vs. DI118h, p=0.023). sColl2-1 was higher for females compared to males (p<0.001) but DI did not affect sColl2-1 in both groups (males: p=0.134, females: p=0.084).

Conclusion: Immobilization by DI resulted in altered serum biomarker concentration of COMP, C2C and CPII in both females and males participants. The mechanosensitive biomarker COMP responded with a substantial decrease of serum concentrations during DI, but returned to BDC levels during recovery. In contrast, sC2C (synthesis) and sCPII (degradation) increased during DI and remained elevated during recovery (C2C: +13%, CPII: +18%), compared to baseline levels. sC2C values were additionally higher for males. The cartilage degradation biomarker Coll2-1 did not respond to DI, however concentrations for females were considerably higher than in males. These findings imply that even a short period of immobilization can have sex-dependent impacts on articular cartilage metabolism.

Funding: Federal Ministry of Economic Affairs and Energy, Germany (DLR 50WB2021, DLR 50WB2022). German Research Foundation (DFG), grant CRC 1483 EmpkinS-Project-ID 442419336 (AML) and FOR2722-Project-ID 407176282 and 384170921 (AN).

Acknowledgements: We sincerely thank our volunteers for participating in the study and the study team at MEDES, Toulouse, France.