Dataset Information

Epigenetic Status of The Human MMP11 Gene Promoter is Altered in Patellar Tendinopathy.

ABSTRACT: Patellar tendinopathy (PT) is a debilitating condition that often affects those who are physically active. Gene variation is known to contribute to human tendinopathy but the role of DNA methylation, as an epigenetic factor, has only recently been discovered. Using a case-control approach, we sought to determine whether differences existed between the methylation status of the MMP11 gene promoter in patellar tendinopathy compared to healthy tendon. We used PCR and pyrosequencing to interrogate the methylation profiles of 4 CpG sites (areas of the genome rich in C/G nucleotides) upstream of the MMP11 gene in DNA from males with PT (n = 10) and those with healthy tendon (n = 10). We also conducted a correlation analysis to establish whether age influenced methylation in the PT patients and controls. We found a significant (p = 0.045) difference in the methylation status of a single CpG site 65 base pairs (bp) upstream of the MMP11 promoter between the PT group and controls. There were no other differences in the extent of MMP11 promoter methylation between the two groups. Interestingly, we also found that in controls the degree of methylation at a second CpG site, 55 bp upstream of the first exon, tentatively correlated (r = 0.77, p = 0.009) with age. However, the correlation did not reach significance when a potential outlier was removed. This is the first study to show an epigenetic alteration to a member of the MMP gene family in human patellar tendinopathy. The data add to our understanding of how epigenetics should be considered when developing appropriate risk models.

SUBMITTER: Rickaby R

PROVIDER: S-EPMC6370951 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenetic Status of The Human <i>MMP11</i> Gene Promoter is Altered in Patellar Tendinopathy.

Rickaby Rebecca R El Khoury Louis Y LY Samiric Tom T Raleigh Stuart M SM

Journal of sports science & medicine 20190211 1

Patellar tendinopathy (PT) is a debilitating condition that often affects those who are physically active. Gene variation is known to contribute to human tendinopathy but the role of DNA methylation, as an epigenetic factor, has only recently been discovered. Using a case-control approach, we sought to determine whether differences existed between the methylation status of the <i>MMP11</i> gene promoter in patellar tendinopathy compared to healthy tendon. We used PCR and pyrosequencing to interr ...[more]

PMID: 30787663

Similar Datasets

Project description:IntroductionThe effect of chronic patellar tendinopathy on tissue function and integrity is currently unclear and underinvestigated. The aim of this cohort comparison was to examine morphological, material, and mechanical properties of the patellar tendon and to extend earlier findings by measuring the ability to store and return elastic energy in symptomatic tendons.MethodsSeventeen patients with chronic (>3 months, VISA-P < 80), inferior pole patellar tendinopathy (24 ± 4 years; male = 12, female = 5) were carefully matched to controls (25 ± 3 years) for training status, pattern, and history of loading of the patellar tendon. Individual knee extension force, patellar tendon stiffness, stress, strain, Young's modulus, hysteresis, and energy storage capacity, were obtained with combined dynamometry, ultrasonography, magnetic resonance imaging, and electromyography.ResultsAnthropometric parameters did not differ between groups. VISA-P scores ranged from 28 to 78 points, and symptoms had lasted from 10 to 120 months before testing. Tendon proximal cross-sectional area was 61% larger in the patellar tendinopathy group than in the control group. There were no differences between groups in maximal voluntary isometric knee extension torque (p = 0.216; d < -0.31) nor in tensile tendon force produced during isometric ramp contractions (p = 0.185; d < -0.34). Similarly, tendon strain (p = 0.634; d < 0.12), hysteresis (p = 0.461; d < 0.18), and strain energy storage (p = 0.656; d < 0.36) did not differ between groups. However, patellar tendon stiffness (-19%; p = 0.007; d < -0.74), stress (-27%; p< 0.002; d < -0.90) and Young's modulus (-32%; p = 0.001; d < -0.94) were significantly lower in tendinopathic patients compared to healthy controls.DiscussionIn this study, we observed lower stiffness in affected tendons. However, despite the substantial structural and histological changes occurring with tendinopathy, the tendon capacity to store and dissipate energy did not differ significantly.

Project description:Purpose: Whole body vibration (WBV) triggers anabolic responses in various tissues, including tendons, without requiring high force production. In this waitlist-controlled equivalence trial, we tested its clinical effectiveness as an alternative treatment for patellar tendinopathy against conventional heavy slow resistance training (HSR). Methods: Thirty-nine patients were randomized to either 3 months of WBV training (n = 13), HSR training (n = 11), or a waitlist control (WLC) group (n = 15). In a partly cross-over design, 14 patients of the WLC group were redistributed to one of the two intervention groups (5 in WBV, 9 in HSR). Pre- and post-intervention testing included pain assessments (VAS), functional limitations (VISA-P), knee extension strength and tendon morphological, mechanical and material properties. Follow-up measurements (VAS, VISA-P) were performed in the WBV and HSR groups 6 months after the intervention. Results: Comparisons with the WLC group revealed significant improvements in VISA-P and VAS scores after HSR (41%, p = 003; 54%, p = 0.005) and WBV (22%, p = 0.022; 56%, p = 0.031) training. These improvements continued until follow-up (HSR: 43%, 56%; WBV: 24%, 37%). Pre-post improvements in VAS scores were equivalent between WBV and HSR groups but inconclusive for the VISA-P score and all pre-test to follow up comparisons. The mid-tendon cross-sectional area was significantly reduced after WBV (-5.7%, p = 0.004) and HSR (-3.0%, p = 0.004) training compared to WLC although the equivalence test between interventions was inconclusive. Conclusion: Whole body vibration improved symptoms typically associated with patellar tendinopathy. This type of intervention is as effective as HSR against maximum pain, although equivalence could not be confirmed for other variables. The beneficial responses to WBV and HSR treatments persisted for 6 months after the end of the intervention. Clinical Trial Registration: https://www.drks.de/drks_web/setLocale_EN.do, identifier DRKS00011338.

Project description:Objectives(1) To determine the association between patellar tendon stiffness and the presence of patellar tendinopathy (PT). (2) To evaluate the reliability of shear-wave elastography (SWE).MethodsParticipants were consecutively enrolled between January 2017 and June 2019. PT was diagnosed clinically and confirmed by either grayscale US or power Doppler US, or both. Controls had no history of anterior knee pain and no clinical signs of PT. Patellar tendon stiffness (kilopascal, kPa) was assessed using SWE. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Reliability analyses included coefficients-of-variation (CV), coefficients-of-repeatability (CR), intraclass correlation coefficient (ICC) for intraobserver and interobserver reliability, and Bland-Altman analysis.ResultsIn total, 76 participants with PT (58 men, mean age 24.4 ± 3.8 years) and 35 asymptomatic controls (16 men, mean age 21.5 ± 3.8 years) were included. Univariate analyses (OR 1.094, 95% CI 1.061-1.128, p < .001) and adjusted multivariate analyses (OR 1.294, 95% CI 1.044-1.605, p = .018) showed that athletes with PT had significantly increased patellar tendon stiffness. ICC for intraobserver reliability was 0.95 (95% CI 0.92-0.97), CR (CV) 12 kPa (10%) and 0.79 (95% CI 0.65-0.88), CR (CV) 18 kPa (21%) for interobserver reliability. Mean differences from Bland-Altman analysis were 5.6 kPa (95% CI 3.1-8.1, p < .001) for intraobserver reliability and 4.6 kPa (95% CI 1.9-7.2, p < .001) for interobserver reliability.ConclusionsPT is associated with significantly higher patellar tendon stiffness. SWE measurements demonstrate excellent intraobserver reliability and good interobserver reliability. Therefore, SWE is a promising tool to implement in longitudinal studies and future studies should evaluate its prognostic value and utility as a monitoring tool in athletes with PT.Key points• Patellar tendon stiffness measured with shear-wave elastography (SWE) is higher in athletes with patellar tendinopathy than in healthy controls, also after adjusting for potential confounders. • Excellent intraobserver reliability and good interobserver reliability were found for the quantitative assessment of patellar tendon stiffness using SWE.

Dataset Information

Epigenetic Status of The Human MMP11 Gene Promoter is Altered in Patellar Tendinopathy.

Publications

Epigenetic Status of The Human <i>MMP11</i> Gene Promoter is Altered in Patellar Tendinopathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets