Five days of immobilization leads to changes in cartilage biomarker concentrations: first data from the Vivaldi study

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Abstract

Introduction: Unloading and immobilization induced by dry immersion (DI) reproduces adequatelymost of the physiological effects of short-term space flight (Tomilovskaya et al., 2019). Articular cartilage is affected by mechanical unloading (Vanwanseele et al., 2002) and the analysis of specific articular cartilage biomarker concentrations was shown to reflect dynamic and quantitative changes in joint remodeling and disease progression at an early stage (Lotz et al., 2013). Previous studies, which examined such biomarkers in response to -6° head-down-tilt bed rest (Liphardt et al., 2017) and microgravity (Niehoff et al., 2016) demonstrated that catabolic processes in articular cartilage were initiated. However, the effects of dry immersion and particularly the impact of unloading models on females regarding changes in cartilage metabolism have not been investigated yet. Therefore, the aim of the study was to analyze the effect of five days immobilization induced by dry immersion on serum
concentrations of the articular cartilage biomarkers C2C (type II collagenase cleavage neoepitope), COMP (cartilage oligomeric matrix protein) and TIMP-2 (tissue inhibitor of metalloproteinases 2) in female healthy adults.

Methods: The "Vivaldi" study is part of a research program of the European Space Agency (ESA) and was conducted at the Institut de Médecine et de Physiologie Spatiales (MEDES) in Toulouse (France). Eighteen healthy female volunteers (29±5 years, 165±6 cm, 59±6 kg) completed four days of baseline data collection (BDC), five days of DI and three days of recovery (R). During DI the volunteers were immersed in a water tank for almost 24 hours per day. A special elastic fabric preserves the volunteers from direct contact with water. Due to the surrounding water the volunteers’ movements, in particular of the lower extremities, were extremely limited. Fasting, venous blood samples were taken on four days: BDC-1, DI3, R+0 and R+2. The volunteers were immobilized during the measurement time points of DI3 and R+0. Serum concentrations of C2C, COMP and TIMP-2 (sC2C, sCOMP and sTIMP-2) were analyzed with commercially available ELISAs. One-way repeated measures ANOVA, following
by LSD post-hoc test, were carried out to detect significant changes in the biomarker concentrations over time.

Results: The sC2C concentration increased significantly from before (BDC-1) to day three of DI (DI3) by +10% (p=0.013). Followed by a further significant increase of +7% from DI3 to R+0 (p=0.02), resulting in an overall increase of +17% compared to baseline (R+0 vs. BDC-1, p=0.002). sC2C levels were still significantly higher during recovery than baseline (R+2 vs. BDC-1, p=0.006). In contrast sCOMP and sTIMP-2 reacted with a significant decrease from BDC-1 to DI3 (p
Conclusions: We could show that five days of DI leads to significant changes in the analyzed cartilage biomarkers. These preliminary results suggest that even a short period of unloading and immobilization has significant effects on the articular cartilage metabolism in healthy female adults, which reinforces the need for proper countermeasures on short- and long-term space flights.

References: Tomilovskaya et al. (2019). Front. Physiol. 10:284; Vanwanseele et al. (2002). Arthritis Rheum. 46(8):2073-2078; Lotz et al. (2013). Ann Rheum Dis. 72(11):1756–1763; Liphardt et al. (2017). J Orthop Res 36(5):1465-1471; Niehoff et al. (2016). Osteoarthritis Cartilage 24(1):144-145

Funding: Federal Ministry of Economic Affairs and Energy, Germany (DLR 50WB2021, DLR 50WB2022)
Original languageEnglish
Title of host publicationHuman Physiology Workshop, 3rd December 2022, Hybrid event
Number of pages1
Place of PublicationKöln
PublisherDeutsches Zentrum für Luft- und Raumfahrt e. V. (DLR)
Publication date03.12.2022
Pages19
Article number15
Publication statusPublished - 03.12.2022
EventHuman Physiology Workshop - Köln, Germany
Duration: 03.12.202203.12.2022
Conference number: 7

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