ArticleJournal of applied physiology (Bethesda, Md. : 1985)2012
Titin-based stiffening of muscle fibers in Ehlers-Danlos Syndrome.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Systematic review of skeletal muscle passive mechanics experimental methodology.Journal of biomechanics · 2021Pooled it
- Unaffected contractility of diaphragm muscle fibers in humans on mechanical ventilation.American journal of physiology. Lung cellular and molecular physiology · 2014Trial
- Sex-specific effects of fatiguing exercise on skeletal muscle passive mechanics are preserved in aging.bioRxiv : the preprint server for biology · 2026Article
- Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Chronic and acute mediators of passive viscoelasticity in human skeletal muscle fibres.Experimental physiology · 2025Article
- Glycerol storage increases passive stiffness of muscle fibers through effects on titin extensibility.The Journal of general physiology · 2025Article
- The distinctive mechanical and structural signatures of residual force enhancement in myofibers.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fatiguing exercise reduces cellular passive Young's modulus in human vastus lateralis muscle.Experimental physiology · 2024Article
- Modulation of Titin and Contraction-Regulating Proteins in a Rat Model of Heart Failure with Preserved Ejection Fraction: Limb vs. Diaphragmatic Muscle.International journal of molecular sciences · 2024Article
- Small Angle X-ray Diffraction as a Tool for Structural Characterization of Muscle Disease.International journal of molecular sciences · 2022Review
- Larger muscle fibers and fiber bundles manifest smaller elastic modulus in paraspinal muscles of rats and humans.Scientific reports · 2021Article
- Muscle ankyrin repeat protein 1 (MARP1) locks titin to the sarcomeric thin filament and is a passive force regulator.The Journal of general physiology · 2021Article
- Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres.International journal of molecular sciences · 2020Article
- Effect of L-Arginine on Titin Expression in Rat Soleus Muscle After Hindlimb Unloading.Frontiers in physiology · 2019Article
- Global Gene Expression Analysis in PKCα-/- Mouse Skin Reveals Structural Changes in the Dermis and Defective Wound Granulation Tissue.The Journal of investigative dermatology · 2015Article
- Removal of immunoglobulin-like domains from titin's spring segment alters titin splicing in mouse skeletal muscle and causes myopathy.The Journal of general physiology · 2014Article
- Impact of titin isoform on length dependent activation and cross-bridge cycling kinetics in rat skeletal muscle.Biochimica et biophysica acta · 2013Article
- Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy.Neurology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivetenascin-X (TNX) is an extracellular matrix glycoprotein whose absence leads to Ehlers-Danlos Syndrome (EDS). TNX-deficient EDS patients present with joint hypermobility and muscle weakness attributable to increased compliance of the extracellular matrix. We hypothesized that in response to the increased compliance of the extracellular matrix in TNX-deficient EDS patients, intracellular adaptations take place in the elastic properties of the giant muscle protein titin.
methodswe performed extensive single muscle fiber mechanical studies to determine active and passive properties in TNX-deficient EDS patients. Gel-electrophoresis, Western blotting, and microarray studies were used to evaluate titin expression and phosphorylation. X-ray diffraction was used to measure myofilament lattice spacing.
resultspassive tension of muscle fibers from TNX-deficient EDS patients was markedly increased. Myofilament extraction experiments indicated that the increased passive tension is attributable to changes in the properties of the sarcomeric protein titin. Transcript and protein data indicated no changes in titin isoform expression. Instead, differences in posttranslational modifications within titin's elastic region were found. In patients, active tension was not different at maximal activation level, but at submaximal activation level it was augmented attributable to increased calcium sensitivity. This increased calcium sensitivity might be attributable to stiffer titin molecules.
conclusionin response to the increased compliance of the extracellular matrix in muscle of TNX-deficient EDS patients, a marked intracellular stiffening occurs of the giant protein titin. The stiffening of titin partly compensates for the muscle weakness in these patients by augmenting submaximal active tension generation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.