Changes in urinary concentrations of the cartilage degradation marker Coll2-1NO2 in response to bed rest immobilization and countermeasures

Anna-Maria Liphardt, Elie-Tino Godonou, Nadja Djalal, Maren Dreiner, Annegret Mündermann, Y. Henrotin, Zaucke Frank, Martina Heer, G Schett, Anja Niehoff

Publikation: Beitrag in Buch/Bericht/KonferenzbandKonferenzbeitrag - Abstract in KonferenzbandForschungBegutachtung


The lack of mechanical stress or joint fluid circulation during immobilization can alter cartilage morphology,
function, and composition resulting in cartilage destruction (Hudelmaier M. et al, 2006; Hagiwara Y. et al, 2009).
Specific immunoassays for a peptide of the triple helix of type II collagen (Coll2-1) and its nitrated form (Coll2-
1NO2) have been developed for measuring cartilage degradation (Henrotin Y. et al, 2004) and radiological
progression of knee OA (Deberg M. A. et al, 2005). This study aims to investigate the effects of 21 days of 6°
head-down tilt bed rest (HDT) combined with nutrition and exercise countermeasures on the urinary levels of Coll
2-1 NO2 in healthy male individuals.
The ESA-funded “Medium duration nutrition and vibration exercise” (MNX)-study was conducted at the Institute
de Médecine et de Physiologie Spatiales (MEDES) in Toulouse, France in a randomized cross-over design with
three campaigns (C1 – 3): 7 days of baseline data collection (BDC), 21 days of HDT, and 7 days of recovery (R+).
A 4-month washout period separated study campaigns. HDT was applied alone (control, CON) or in combination
with resistive vibration exercise (RVE) or RVE + whey & bicarbonate supplementation, NeX) in twelve healthy
male subjects (age 34.2 ± 8.3 years; BMI 22.4 ± 1.7 kg/m²). Urinary (u) Coll2-1NO2 concentrations were
measured by immunoassay (Artialis, Liège, Belgium) in 24hrs urines at BDC -3 to -1, HDT2, HDT3, HDT5,
HDT7, HDT14, HDT21, R+1, and R+6. For the regression model, BDC was calculated as the mean of BDC -3 to
-1. Linear Mixed-Effects Models were used to detect significant changes in uColl 2-1 NO2 (nM), considering
time points and countermeasures as predictors.
At baseline (BDC-3) of campaign 1, uColl2-1NO2 (mean (sd)) was 0.108 (0.04) nM for all study participants.
Time points (p=0.011) and countermeasures (p<0.001) had a significant effect on uColl2-1NO2. More
specifically, overall (main effect) uColl2-1 NO2 was lower (Figure 1.A) on R+1 compared to BDC by 47.3% (β=-
0.04, 95%CI: -0.08 – -0.01, p=0.008); when the countermeasure is NEX (Figure 1.B), uColl 2-1 NO2
concentrations were increased by 53.7% (β=0.04, 95%CI=0.03 – 0.06, p<0.001).
Figure 1: Mean urine concentration of Coll 2-1 NO2 in all groups over time (A), and by intervention (B).
Three weeks of bed rest immobilization resulted in lower levels of uColl 2-1NO2 at R+1 day (vs. BDC),
potentially reflecting the oxidative-stress related cartilage remodeling. The nutrition countermeasure (whey &
bicarbonate supplementation) in combination with resistive vibration exercise (NEX) lead to higher Coll 2-1NO2
urinary levels compared to the control intervention. While the seen difference between NEX and other
interventions (CON, RVE) is notable during bed rest, the overall observed bed rest effect on Coll2-1NO2 is not
as prominent as previously reported in other cartilage biomarkers (Liphardt et al. 2009, 2018, 2020). Coll2-1NO2
may not be as sensitive to mechanical loading as other markers which is in line with the previously observed
response of uColl2-1NO2 in response to marathon running.
Hudelmaier M. et al, 2006, J Musculoskelet Neuronal Interact 6, 284–290. Hagiwara Y. et al, 2009, J Orthop Res. 27, 236–
Henrotin, Y. et al, 2004, Biorheology, 41, 543–547. Deberg, M. A. et al, 2005, Osteoarthritis Cartilage, 13, 1059–1065.
Liphardt et al. 2009, Osteoarthritis Cartilage. Dec;17(12):1598-603. Liphardt et al. 2018, J Orthop Res. May;36(5):1465-1471.
Liphardt et al. 2020, J Orthop Res. Nov;38(11):2373-2382. Henrotin et al. 2013, Springerplus Dec;2(1):92.
TitelChanges in urinary concentrations of the cartilage degradation marker Coll2-1NO2 in response to bed rest immobilization and countermeasures
PublikationsstatusVeröffentlicht - 2023
VeranstaltungConference of the International Society for gravitational physiology - University of Antwerp, Antwerp, Belgien
Dauer: 02.07.202307.07.2023
Konferenznummer: 42


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