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Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study.

ABSTRACT: BACKGROUND:An early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis. A secondary aim was to assess whether prior knee injury or subjective patient-reported outcomes at baseline (BL) were associated with articular cartilage changes. Nineteen volleyball players (mean age 46.5?±?4.9?years, 47% male) with a 30-year history of regular high impact training were recruited. The serum biomarkers Cpropeptide of type II procollagen (CPII), cartilage oligomeric matrix protein (COMP), collagenase generated carboxy-terminal neoepitope of type II collagen (sC2C), cartilage intermediate layer protein 2 (CILP-2), and the urine biomarkers C-telopeptide of type II collagen (CTX-II) and collagenase-generated peptide(s) of type II collagen (C2C-HUSA) were assessed at BL and at 2 year follow up (FU). Femorotibial cartilage thinning, thickening and absolute thickness change between BL and FU was evaluated from magnetic resonance imaging. Subjective clinical status at BL was evaluated by the International Knee Documentation Committee Subjective Knee Form and the Short-Form 36 Physical Component Score. RESULTS:CILP-2 was significantly higher at FU and linearly associated with the absolute cartilage thickness change during the experimental period. Prior injury was a predictor of increased absolute cartilage thickness change. CONCLUSION:Measuring the change in the cartilage biomarker CILP-2 might be a valid and sensitive method to detect early development of knee osteoarthritis as CILP-2 appears to be related to cartilage thickness loss in certain individuals with increased risk of developing knee osteoarthritis. Prior knee injury may be predictive of increased articular cartilage thickness change.

SUBMITTER: Boeth H

PROVIDER: S-EPMC6499840 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study.

Boeth Heide H Raffalt Peter C PC MacMahon Aoife A Poole A Robin AR Eckstein Felix F Wirth Wolfgang W Buttgereit Frank F Önnerfjord Patrik P Lorenzo Pilar P Klint Cecilia C Pramhed Anna A Duda Georg N GN

Journal of experimental orthopaedics 20190503 1

<h4>Background</h4>An early detection of Osteoarthritis is urgently needed and still not possible until today. The aim of the study was to assess whether molecular biomarkers of cartilage turnover are associated with longitudinal change in knee cartilage thickness during a 2 year period in individuals with increased risk of developing knee osteoarthritis. A secondary aim was to assess whether prior knee injury or subjective patient-reported outcomes at baseline (BL) were associated with articula ...[more]

PMID: 31053993

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Project description:BACKGROUND:Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee joints at different radiographic stages and pain categories with levels of uCTX-II and biomarkers of bone resorption and formation. METHODS:Baseline data of two randomised clinical trials (NCT00486434 and NCT00704847) in patients with radiographic OA and presence of pain were analysed post hoc. A subgroup with available urine samples and evaluable radiographs for both knees (N = 1241) was analysed. Urine CTX-I, urine CTX-II and serum osteocalcin were analysed for associations with combined Kellgren-Lawrence (KL) scores, gender and pain for both knees to assess the contribution of joints at different stages. RESULTS:Pain, BMI, age, gender and KL grade were all significantly associated with uCTX-II. The association between pain and CTX-II appeared to be driven by weight-bearing pain. The level of uCTX-II incrementally increased with higher radiographic severity of each knee. Levels of bone markers CTX-I and osteocalcin were both significantly associated with BMI and gender, but neither were associated with radiographic severity. Biomarker levels between male or female groups of identical KL scores were found to be higher in females compared to males in some but not all KL score groups. CONCLUSIONS:These results indicate that levels of uCTX-II are independently associated with radiographic severity of OA and pain intensity. CTX-II was associated with weight-bearing pain, but not non-weight-bearing pain, independent of co-variates. Bilateral OA knee joints appear to contribute to uCTX-II levels in an incremental manner according to radiographic severity of single joints. The data suggest that biomarker differences between genders should be taken into account when evaluating these markers in the context of structural features of OA.

Project description:SignificanceArticular cartilage exhibits a zonal architecture, comprising three distinct zones: superficial, middle, and deep. Collagen fibers, being the main solid constituent of articular cartilage, exhibit unique angular and size distribution in articular cartilage zones. There is a gap in knowledge on how the unique properties of collagen fibers across articular cartilage zones affect the scattering properties of the tissue.AimThis study hypothesizes that the structural properties of articular cartilage zones affect its scattering parameters. We provide scattering coefficient and scattering anisotropy factor of articular cartilage zones in the spectral band of 400 to 1400 nm. We enumerate the differences and similarities of the scattering properties of articular cartilage zones and provide reasoning for these observations.ApproachWe utilized collimated transmittance and integrating sphere measurements to estimate the scattering coefficients of bovine articular cartilage zones and bulk tissue. We used the relationship between the scattering coefficients to estimate the scattering anisotropy factor. Polarized light microscopy was applied to estimate the depth-wise angular distribution of collagen fibers in bovine articular cartilage.ResultsWe report that the Rayleigh scatterers contribution to the scattering coefficients, the intensity of the light scattered by the Rayleigh and Mie scatterers, and the angular distribution of collagen fibers across tissue depth are the key parameters that affect the scattering properties of articular cartilage zones and bulk tissue. Our results indicate that in the short visible region, the superficial and middle zones of articular cartilage affect the scattering properties of the tissue, whereas in the far visible and near-infrared regions, the articular cartilage deep zone determines articular cartilage scattering properties.ConclusionThis study provides scattering properties of articular cartilage zones. Such findings support future research to utilize optical simulation to estimate the penetration depth, depth-origin, and pathlength of light in articular cartilage for optical diagnosis of the tissue.

Project description:BackgroundProteomics is an emerging field in the study of joint disease. Our two aims with this pilot analysis were to compare healthy human knee articular cartilage with meniscus, two tissues both known to become affected in the osteoarthritic disease process, and to compare two mass spectrometry (MS)-based methods: data-dependent acquisition (DDA) and data-independent acquisition (DIA).MethodsHealthy knee articular cartilage taken from the medial tibial condyle and medial meniscus samples taken from the body region were obtained from three adult forensic medicine cases. Proteins were extracted from tissue pieces and prepared for MS analysis. Each sample was subjected to liquid chromatography (LC)-MS/MS analysis using an Orbitrap mass spectrometer, and run in both DDA and DIA mode. Linear mixed effects models were used for statistical analysis.ResultsA total of 653 proteins were identified in the DDA analysis, of which the majority was present in both tissue types. Only proteins with quantitation information in both tissues (n = 90) were selected for more detailed analysis, of which the majority did not statistically significantly differ in abundance between the two tissue types, in either of the MS analyses. However, 21 proteins were statistically significantly different (p < 0.05) between meniscus and cartilage in the DIA analysis. Out of these, 11 proteins were also significantly different in the DDA analysis. Aggrecan core protein was the most abundant protein in articular cartilage and significantly differed between the two tissues in both methods. The corresponding protein in meniscus was serum albumin. Dermatopontin exhibited the highest meniscus vs articular cartilage ratio among the statistically significant proteins. The DIA method led to narrower confidence intervals for the abundance differences between the two tissue types than DDA.ConclusionsAlthough articular cartilage and meniscus had similar proteomic composition, we detected several differences by MS. Between the two analyses, DIA yielded more precise estimates and more statistically significant different proteins than DDA, and had no missing values, which makes it preferable for future LC-MS/MS analyses.

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Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study.

Publications

Association between changes in molecular biomarkers of cartilage matrix turnover and changes in knee articular cartilage: a longitudinal pilot study.

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