Collagen Type III and VI Turnover in Response to Long-Term Immobilization

PLoS One. 2015 Dec 7;10(12):e0144525. doi: 10.1371/journal.pone.0144525. eCollection 2015.


Background: Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization.

Methods: In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage.

Results: Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization.

Conclusion: The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bed Rest*
  • Biomarkers / blood*
  • Case-Control Studies
  • Collagen Type III / blood*
  • Collagen Type VI / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Exercise Therapy*
  • Follow-Up Studies
  • Humans
  • Immobilization / methods*
  • Male
  • Muscle Strength / physiology*
  • Prognosis
  • Young Adult


  • Biomarkers
  • Collagen Type III
  • Collagen Type VI

Grant support

The biomarker portion of the study was supported by the Danish Research Foundation. AFN is funded in part by Nordic Bioscience through industrial post doc collaboration with the Department of Sports Medicine Copenhagen and the Danish Advanced Technology Foundation. Nordic Bioscience provided support in the form of salaries for authors SS, KH, MAK and IB. The funders did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.