ArticleNature communications2023
Age-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis.Bioscience reports · 2024Pooled it
- Uncovering the "riddle of femininity" in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment.Osteoarthritis and cartilage · 2023Pooled it
- Nuclear mechanotransduction: tools for mechanical perturbation and chromatin characterization.Nucleus (Austin, Tex.) · 2026Review
- Exercise enhances aged chondrocyte health through microRNA-29-enriched extracellular vesicles.Nature aging · 2026Article
- Menopausal timing and senescent-immune coupling in age-related lobular involution of the human breast: a longitudinal cohort study.EBioMedicine · 2026Article
- Network Model to Predict Age-Related Transcriptional Reprogramming.Aging cell · 2026Article
- Article
- From disease model to therapeutic insight: An engineered hydrogel reveals the role of matrix viscous dissipation in intervertebral disc degeneration.Bioactive materials · 2026Article
- Substrate stiffness dictates unique paths towards proliferative arrest in WI-38 cells.GeroScience · 2026Article
- cGAS-STING/HMGB1-mediated senescence induced by LRRK2 accelerates cartilage degeneration in osteoarthritis.Cell death & disease · 2026Article
- Estradiol treatment induces both shared and unique gene regulation and networks in adipose cell types of gonadectomized obese XX and XY mice.Biology of sex differences · 2026Article
- Regulatory Potential of piRNAs TargetingGenes · 2026Article
- Nanotherapeutic Strategies for Osteoarthritis: Targeting Aging, Metabolism and Inflammation.International journal of nanomedicine · 2026Review
- Nano MiRNA-Functionating Tetrahedral Framework Nucleic Acid for Cartilage-Targeted Ferritinophagy Modulation to Attenuate Temporomandibular Joint Osteoarthritis.Small science · 2026Article
- Engineering Aging: Approaches to Model and Deconstruct Biological Complexity.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Sex differences in the pathogenesis of degenerative knee osteoarthritis: a comparative transcriptomics analysis.Frontiers in aging · 2026Article
- Multimodal mechanoregulation strategies towards tissue regeneration.Mechanobiology in medicine · 2025Review
- Nanotechnology-driven strategies for gene therapy of arthritis.Materials today. Bio · 2025Review
- Increased TNN in Knee Osteoarthritis Accelerates Cartilage Damage via the Negative Regulation of AMPK-PPARγ Signalling.Journal of cellular and molecular medicine · 2025Article
- Machine-learning models based on histological images from healthy donors identify imageQTLs and predict chronological age.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Extracellular matrix stiffening is a quintessential feature of cartilage aging, a leading cause of knee osteoarthritis. Yet, the downstream molecular and cellular consequences of age-related biophysical alterations are poorly understood. Here, we show that epigenetic regulation of α-Klotho represents a novel mechanosensitive mechanism by which the aged extracellular matrix influences chondrocyte physiology. Using mass spectrometry proteomics followed by a series of genetic and pharmacological manipulations, we discovered that increased matrix stiffness drove Klotho promoter methylation, downregulated Klotho gene expression, and accelerated chondrocyte senescence in vitro. In contrast, exposing aged chondrocytes to a soft matrix restored a more youthful phenotype in vitro and enhanced cartilage integrity in vivo. Our findings demonstrate that age-related alterations in extracellular matrix biophysical properties initiate pathogenic mechanotransductive signaling that promotes Klotho promoter methylation and compromises cellular health. These findings are likely to have broad implications even beyond cartilage for the field of aging research.
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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.