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Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men.

ABSTRACT: BACKGROUND: Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain is reflected by peptide biomarkers derived from type VI collagen processing released in the circulation. METHODS: In order to test this hypothesis, we set out to develop an ELISA assay against an type VI collagen N-terminal globular domain epitope (IC6) and measured the levels of IC6 and an MMP-generated degradation fragment of collagen 6, (C6M) in a human immobilization-remobilization study setup with young (n?=?11) and old (n?=?9) men. They were subjected to 2 weeks of unilateral lower limb immobilization followed by 4 weeks of remobilization including thrice weekly resistance training, using the contralateral leg as internal controls. Subjects were sampled for strength, quadriceps muscle volume and blood at baseline (PRE), post-immobilization (2W), and post-remobilization (4W). Blood were subsequently analyzed for levels of the C6M and IC6 biomarkers. We subsequently tested if there was any correlation between C6M, IC6, or the C6M/IC6 ratio and muscle mass or strength at baseline. We also tested whether there was any relation between these biomarkers and changes in muscle mass or strength with immobilization or remobilization. RESULTS: The model produced significant loss of muscle mass and strength in the immobilized leg. This loss was bigger in young subjects than in elderly, but whereas the young recovered almost fully, the elderly had limited regrowth of muscle. We found a significant correlation between IC6 and muscle mass at baseline in young subjects (R (2)?=?0.6563, p?=?0.0045), but none in the elderly. We also found a significant correlation between C6M measured at the 4W time point and the change in muscle mass during remobilization, again only manifesting in the young men(R (2)?=?0.6523, p?=?0.0085). This discrepancy between the young and the elderly may be caused in part by much smaller changes in muscle mass in the elderly and partly by the relative small sample size. CONCLUSION: While we cannot rule out the possibility that these biomarkers in part stem from other tissues, our results strongly indicate that these markers represent novel biomarkers of muscle mass or change in muscle mass in young men.

SUBMITTER: Nedergaard A

PROVIDER: S-EPMC3830008 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men.

Nedergaard Anders A Sun Shu S Karsdal Morten A MA Henriksen Kim K Kjær Michael M Lou Yunyun Y He Yi Y Zheng Qinlong Q Suetta Charlotte C

Journal of cachexia, sarcopenia and muscle 20130813 4

<h4>Background</h4>Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain is reflected by peptide biomarkers derived from type VI collagen processing released in the circulation.<h4>Methods</h4>In order to test this hypothesis, we set out to develop an ELISA assay ag ...[more]

PMID: 23943593

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Project description:BackgroundSystemic sclerosis (SSc) is a rare autoimmune disease characterized by microvasculopathy, autoantibody production, and fibrosis of the skin and internal organs. Disrupted collagen turnover in SSc leads to excessive collagen accumulation, but the remodeling of type VII collagen, a key component of the skin's basement membrane, is not well understood. This study investigates type VII collagen turnover in SSc by measuring serum levels of its formation (PRO-C7) and degradation (C7M) biomarkers and characterizing their association with other ECM biomarkers and clinical manifestations.MethodsAn automated immunoassay, PRO-C7, was developed to quantify type VII collagen formation. Additionally, C7M, along with type III, IV, and VI collagen turnover biomarkers, were analyzed in a post-hoc study of SSc patients. The normality of all variables of interest was assessed using the Shapiro-Wilk test. Spearman's correlation and Welch's T-testtests were used to assess associations and differences in biomarker levels between SSc patients and healthy controls. A linear regression model was used to assess the relationship between biomarker levels and the modified Rodnan skin score (mRSS).To control the type I errors in multiple comparisons, the Bonferroni Correction was applied to adjust the significance levels.ResultsResults showed significantly elevated levels of type VII and VI collagen turnover biomarkers in SSc patients and controls. PRO-C3 and PRO-C6 levels were significantly correlated with mRSS score (R2 = 0.156, p = 0.0004; R2 = 0.222, p < 0.0001 respectively), while PRO-C7 and C7M were not. Moderate but significant correlations were observed between both PRO-C7 and C7M with C-reactive protein and Erythrocytes sedimentation rate, respectively (ρ = 0.39, p = 0.0006; ρ = 0.24 p = 0.045 for PRO-C7; ρ = 0.31, p = 0.0076; ρ = 0.28, p = 0.014 for C7M). C7M showed a significant correlation with type III, type IV, type VI collagen formation and degradation biomarkers, while PRO-C7 correlated significantly only with PRO-C6 and C6M. Furthermore, C7M levels were higher in SSc patients with renal dysfunction, and elevated PRO-C7 levels were associated with anti-dsDNA, while lower PRO-C7 levels were linked to capillary abnormalities in SSc.ConclusionsIn conclusion, PRO-C7 and C7M, reflecting type VII collagen turnover, show promise as new serological biomarkers for SSc.

Project description:Dairy products and impact exercise have previously been identified to be independently beneficial for bone mineral properties, however, it is unknown how the combination of these two osteogenic interventions may alter acute bone turnover. Using a randomized crossover design, we compared the acute effects of consuming milk vs. an isoenergetic carbohydrate control beverage on bone biomarkers following loading exercise. Thirteen healthy female participants (Age = 20.3 ± 2.3y; BMI = 21.0 ± 1.1 kg/m2) consumed either 550 mL of 0% skim white milk (MILK) or 52.7 g of maltodextrin in 550 mL of water (CHO), both 5 min and 1 h following completion of a combined plyometric (198 impacts) and resistance exercise (3-4 sets/exercise, 8-12 reps/set, ∼75% 1-RM) bout. Venous blood samples were obtained pre-exercise, and 15 min, 75 min, 24 h and 48 h post-exercise to assess serum concentrations of bone resorption biomarkers, specifically carboxyl-terminal crosslinking telopeptide of type I collagen (CTX), receptor activator nuclear factor kappa-β ligand (RANKL), and sclerostin (SOST), as well as bone formation biomarkers, specifically osteoprotegerin (OPG) and osteocalcin (OC). When absolute biomarker concentrations were examined, there were no interaction or group effects for any biomarker, however, there were main time effects (p < 0.05) for RANKL, SOST, and OC, which were lower, and the OPG: OPG/RANKL ratio, which was higher at 75 min post-exercise compared with baseline in both conditions. In addition to assessing absolute biomarker concentrations at specific timepoints, we also evaluated the relative (% change) cumulative post-exercise response (75 min to 48 h) using an area under the curve (AUC) analysis. This analysis showed that the relative post-exercise CTX response was significantly lower in the MILK compared to the CHO condition (p = 0.03), with no differences observed in the other biomarkers. These results show that while milk does not appear to alter absolute concentrations of bone biomarkers compared to CHO, it may attenuate relative post-exercise bone resorption (i.e., blunt the usual catabolic response to exercise).

Project description:BackgroundThe collagen-rich tumor stroma plays a crucial role in biliary tract cancer (BTC). Collagen biomarkers of type I collagen (reC1M), type III collagen (PRO-C3), type IV collagen (C4G), type VIII collagen (PRO-C8), type XI collagen (PRO-C11), type XVII collagen (PRO-C17) and type VIII collagen (TUM) may be used as potential non-invasive biomarkers.MethodsWe measured the seven biomarkers of collagen turnover in sera of 72 patients with BTC at baseline and after first and second chemotherapy cycle (CTX). Markers were also assessed in sera of 50 healthy controls and compared to levels of patients at baseline. The diagnostic and prognostic value of the markers was evaluated for overall survival (OS) and progression-free survival (PFS).ResultsPatients had a median age of 65 years (IQR 57-70), while healthy controls were younger, with a median age of 46 years (IQR 38-54). The majority of patients (62%) were diagnosed with intrahepatic bile duct adenocarcinoma. Except C4G, all collagen turnover markers were significantly (p < 0.001) increased in serum from patients with BTC compared to healthy controls. PRO-C3 was the best marker to discriminate between patients with BTC and controls, reaching an area under a receiver operating characteristic (AUROC) of 0.98 (95% CI 0.95; 0.99) with a sensitivity (92%) and specificity (94%) balanced cutoff of 77.3 ng/ml. Patients with high levels (cohort separated by median split) of PRO-C8 (HR 2.85, 95% CI 1.42; 5.73) followed by C3M (HR 2.33, 95% CI 1.2; 4.5), PRO-C3 (HR 3.09, 95% CI 1.5; 6.36) and CA 19-9 (HR 2.52, 95% CI 1.37; 4.64) as reference biomarker had a shorter OS. Notably, only the novel marker PRO-C8 was also predictive of PFS (HR 3.26, 95% CI 1.53; 6.95). Associations with survival outcomes remained significant after adjusting for relevant risk factors (CA 19-9 and CEA at baseline, age, presence of metastases, weight, height and gender).ConclusionThe collagen turnover markers PRO-C8, C3M, PRO-C3 and the established biomarker CA 19-9 were prognostic for OS in patients with BTC while only PRO-C8 was also predictive for PFS. PRO-C3 showed the best diagnostic performance to discriminate between patients with BTC and controls.Trial registrationTrial registration number and date of registration NCT00661830 (NCT number) 15 April 2008 Trial registry The complete registry can found under: https://clinicaltrials.gov/study/NCT00661830?tab=table#administrative-information (last accessed 01/2025) Principal investigator and study sponsor Markus Moehler, MD Johannes Gutenberg University Mainz.

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Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men.

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Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men.

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