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Differences in biomarkers of cartilage matrix turnover and their changes over 2 years in adolescent and adult volleyball athletes.

ABSTRACT: BACKGROUND:This study aimed the feasibility to assess longitudinal changes in biomarkers of cartilage turnover and to determine their relationship with patient-rated outcomes over 2 years in volleyball athletes. METHODS:Thirty-seven athletes were studied: 18 adolescents (age 15.9 ± 0.64 years) in a 2-year intensive volleyball training program and 19 adult recreational volleyball players (age 46.5 ± 4.9 years). Blood and serum samples were taken at baseline (BL) and 2-year follow-up (FU). Subjects completed the International Knee Documentation Committee (IKDC) Subjective Knee Form and the Short-Form 36 (SF-36) at BL. RESULTS:Thirteen adolescents (72%) had open growth plates at BL (BL open adolescents), the rest had closed growth plates at BL (BL closed adolescents), and all but one adolescent had closed growth plates at FU as assessed by MRI. BL open and closed adolescents had greater levels of the cartilage degradation-based biomarkers 45 mer collagenase peptide of type II collagen (C2C-HUSA) and C-telopeptide of type II collagen (CTX-II) than adults. BL open adolescents showed decreases in C2CHUSA, collagen synthesis marker C-propeptide of type II procollagen (CPII), and CTXII, and adults showed increases in cartilage intermediate layer protein 2 (CILP-2) and C2C-HUSA. In adolescents, IKDC scores were correlated with CPII changes. In adults, SF-36 Physical Component Scores were correlated with cartilage oligomeric matrix protein (COMP) changes. CONCLUSION:Significant differences in biomarker levels over time show the feasibility to assess their changes. Greater levels of C2C-HUSA and CTX-II in adolescents than in adults may reflect increased cartilage turnover in response to higher joint loading. CPII and COMP may be more reflective of subjective patient outcomes. These biomarkers may thus be useful in assessing mechanical loading-induced cartilage changes, their associated symptoms, and Osteoarthritis risk in athletes.

SUBMITTER: Boeth H

PROVIDER: S-EPMC5321644 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Differences in biomarkers of cartilage matrix turnover and their changes over 2 years in adolescent and adult volleyball athletes.

Boeth Heide H MacMahon Aoife A Poole A Robin AR Buttgereit Frank F Önnerfjord Patrik P Lorenzo Pilar P Klint Cecilia C Pramhed Anna A Duda Georg N GN

Journal of experimental orthopaedics 20170223 1

<h4>Background</h4>This study aimed the feasibility to assess longitudinal changes in biomarkers of cartilage turnover and to determine their relationship with patient-rated outcomes over 2 years in volleyball athletes.<h4>Methods</h4>Thirty-seven athletes were studied: 18 adolescents (age 15.9 ± 0.64 years) in a 2-year intensive volleyball training program and 19 adult recreational volleyball players (age 46.5 ± 4.9 years). Blood and serum samples were taken at baseline (BL) and 2-year follow-u ...[more]

PMID: 28229430

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Project description:BackgroundAn 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.ResultsCILP-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.ConclusionMeasuring 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.

Project description:BackgroundSprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix (ECM) production. To gain further insight into the process of sprifermin in the cartilage tissue, this study aimed at investigating the ECM turnover of articular cartilage explants in a longitudinal manner.MethodsBovine full-depth articular cartilage explants were stimulated with sprifermin or placebo at weekly intervals, similar to the dosing regimen used in clinical trials. Pre-culturing with oncostatin M and tumour necrosis factor-α, was also used to induce an inflammatory state before treatment. Metabolic activity was measured using AlamarBlue, and chondrocyte proliferation was visualized by immuno-histochemical detection of proliferating cell nuclear antigen. ECM turnover was quantified by biomarker ELISAs; ProC2 reflecting type II collagen formation, CS846 reflecting aggrecan formation, active MMP9, C2M and AGNx2 reflecting matrix metalloproteinase activity, and AGNx1 reflecting aggrecanase activity.ResultsSprifermin was able to reach the chondrocytes through the extracellular matrix, as it increased cell proliferation and metabolic activity of explants. ProC2 and CS846 was dose-dependently increased (P < 0.05) by sprifermin compared to placebo, while C2M and AGNx2 were unaffected, active MMP9 was slightly decreased, and AGNx1 was slightly increased. Over the course of treatment, the temporal order of ECM turnover responses was AGNx1, then ProC2, followed by CS846 and MMP9. Pro-inflammatory activation of the explants diminished the ECM turnover responses otherwise observed under non-inflammatory conditions.ConclusionsThe data suggest that sprifermin has chondrogenic effects on articular cartilage ex vivo, exerted through a sequential process of ECM turnover; aggrecan degradation seems to occur first, while type II collagen and aggrecan production increased at a later time point. In addition, it was observed that these chondrogenic effects are dependent on the inflammatory status of the cartilage prior to treatment.

Project description:BackgroundCompared with the normal adult population, athletes of several sport disciplines, such as endurance sports, ball sports, cycling and swimming, have higher use of over-the-counter analgesics (OTC analgesics). The aim of this study was to describe the epidemiology of OTC analgesic use in volleyball players as a typical competitive sport discipline. One particular focus was placed on the analysis whether the athletes' use of OTC analgesics was influenced by their performance motivation.MethodsA cross-sectional survey among amateur volleyball players was carried out using a web-based sports questionnaire. The study included athletes of both sexes, 18 years and older, currently playing in a German volleyball league. The athletes' sport-related complaints were evaluated regarding the use of OTC analgesics. The use of OTC analgesics by athletes was compared with their performance motivation, based on the "Achievement Motives Scale - Sport" (AMS-Sport) questionnaire.ResultsThe analysis of 114 completed questionnaires of amateur athletes revealed that the use of OTC analgesics was sex dependent, with a higher prevalence of use in female players (60%) versus male players (38%). The main reasons for consumption of OTC analgesics were pain in the head, knee and shoulder. The most frequently taken drug was ibuprofen, most often taken at competitions and over a period of 4 years (median). The analysis of the AMS-Sport questionnaire revealed that a logistic regression model for estimating the probability of drug use can be explained by the factors hope of success and years of playing practise in female players but not male players. In females, an increase in the factor hope of success resulted in a lower probability of OTC analgesic use, while an increase in years of playing practise resulted in a higher probability of use.ConclusionThe average duration that volleyball players in this study took OTC analgesics was higher than that of the German population, and OTC analgesic use was more prevalent in female than male volleyball players. Thus, to reduce the prevalence of OTC analgesic use, educational programs should be implemented in sports teams; and, to reduce direct and indirect social pressure, sports teams should also receive sex-specific psychological support.

Project description:Serum cartilage oligomeric matrix protein (sCOMP) is a biomarker for cartilage degradation. Patient-reported outcomes (PRO) are used to document postinjury recovery and may be used to prospectively identify changes in the course of a season. It is unknown what effect intense, continuous physical activity has on sCOMP levels and PRO values in athletes over the duration of a soccer season. Hypothesis/The purpose of this study was to longitudinally document sCOMP levels and to determine whether changes in PROs occur in collegiate soccer athletes during a season. The hypotheses tested were that sCOMP levels and PRO scores would remain stable over the duration of the spring soccer season.Case series; level of evidence, 4.Twenty-nine National Collegiate Athletic Association Division-I soccer athletes (18 men, 11 women; age, 19.6 ± 1.2 years; height, 177.8 ± 7.4 cm; mass, 73.8 ± 10.2 kg) participated in 3 (pre-[T(1)], mid-[T(2)], and postseason [T(3)]) data collection sessions. Subjects were included if they were participants in the spring soccer season and were free of severe knee injury at the time of data collection. At each session, subjects completed PROs (Lysholm, International Knee Documentation Committee scores) before serum collection.For sCOMP (ng/mL), there was a significant effect for time, with significant increases at T(2) (1723.5 ± 257.9, P < .001) and T(3) (1624.7 ± 231.6, P = .002) when compared with T(1)(1482.9 ± 217.9). For each of the PROs, there was a significant effect for time from T(1)-T(3), and at T(2)-T(3) for the IKDC.These data indicate sCOMP levels increased as athletes reported an increased level of function over time. However, the differences in sCOMP levels did not reach the calculated minimal detectable change (MDC) value and the differences in PRO scores did not reach previously calculated MDC values. It is unclear whether these increases in sCOMP levels were caused by an increase in cartilage matrix breakdown or turnover. Even though these elevations may not be clinically meaningful, this biomarker may have the potential to be used for future research studies investigating the effects of exercise on overall joint health in longitudinal studies. In addition, these results indicate fluctuations in sCOMP occur during a competitive season and must be taken into consideration for future biomarker studies.

Project description:Sport concussions can be difficult to diagnose and if missed, they can expose athletes to greater injury risk and long-lasting neurological disabilities. Discovery of objective biomarkers to aid concussion diagnosis is critical to protecting athlete brain health. To this end, we performed targeted proteomics on plasma obtained from adolescent athletes suffering a sports concussion. A total of 11 concussed male athletes were enrolled at our academic Sport Medicine Concussion Clinic, as well as 24 sex-, age- and activity-matched healthy control subjects. Clinical evaluation was performed and blood was drawn within 72 h of injury. Proximity extension assays were performed for 1,472 plasma proteins; a total of six proteins were considered significantly different between cohorts (P < 0.01; five proteins decreased and one protein increased). Receiver operating characteristic curves on the six individual protein biomarkers identified had areas-under-the-curves (AUCs) for concussion diagnosis ≥0.78; antioxidant 1 copper chaperone (ATOX1; AUC 0.81, P = 0.003), secreted protein acidic and rich in cysteine (SPARC; AUC 0.81, P = 0.004), cluster of differentiation 34 (CD34; AUC 0.79, P = 0.006), polyglutamine binding protein 1 (PQBP1; AUC 0.78, P = 0.008), insulin-like growth factor-binding protein-like 1 (IGFBPL1; AUC 0.78, P = 0.008) and cytosolic 5'-nucleotidase 3A (NT5C3A; AUC 0.78, P = 0.009). Combining three of the protein biomarkers (ATOX1, SPARC and NT5C3A), produced an AUC of 0.98 for concussion diagnoses (P < 0.001; 95% CI: 0.95, 1.00). Despite a paucity of studies on these three identified proteins, the available evidence points to their roles in modulating tissue inflammation and regulating integrity of the cerebral microvasculature. Taken together, our exploratory data suggest that three or less novel proteins, which are amenable to a point-of-care immunoassay, may be future candidate biomarkers for screening adolescent sport concussion. Validation with protein assays is required in larger cohorts.

Project description:The growth plate contains resting and proliferating chondrocytes in its upper zones (UGP) and maturing and hypertrophic chondrocytes in its lower zones (LGP), but the mechanisms by which it operates to sustain skeletal growth are not fully clear. Retinoid signaling was previously found to be nearly absent in UGP, but to be much stronger in LGP coincident with hypertrophy, extracellular matrix turnover and endochondral bone formation. To determine whether such distinct signaling levels and phenotypic events reflect different endogenous retinoid levels, the upper two-thirds and lower one-third of rabbit rib growth plates were microsurgically isolated and processed for ultrasensitive retinoid LC-tandem MS quantification. Indeed, the UGP samples contained only about a 0.6 nm concentration of all-trans-retinoic acid (atRA) that is the most active natural retinoid in tissues, whereas LGP samples contained nearly 3-fold higher atRA levels (about 1.8 nM). Perichondrium was quite rich in atRA (about 4.9 nM). Interestingly, the levels of retinol, the major but inactive atRA precursor, were similar in all tissues (1.1-1.6 μM), suggesting that the distinct atRA levels in UGP and LGP reflect different retinoid anabolic capacity. Indeed, RALDH2 and CRABP1 transcript levels were much higher in LGP than UGP samples. To determine the minimum effective atRA concentration, chondrogenic cells transfected with a retinoic acid response element (RARE)-luc reporter plasmid were treated with different concentrations of exogenous atRA (0-100 nM). About 3 nm atRA was needed to elicit appreciable RARE-luc reporter activity and to decrease proteoglycan synthesis and activity of an aggrecan enhancer reporter plasmid. In sum, the data indicate that (i) the endogenous levels of atRA are significantly higher in hypertrophic than upper zones of growth plate; (ii) such difference likely reflects distinct retinoid anabolic capacity; and (iii) importantly, atRA levels in hypertrophic portion are within effective ranges to elicit retinoid signaling and action, but those in upper zones are not.

Dataset Information

Differences in biomarkers of cartilage matrix turnover and their changes over 2 years in adolescent and adult volleyball athletes.

Publications

Differences in biomarkers of cartilage matrix turnover and their changes over 2 years in adolescent and adult volleyball athletes.

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