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Overuse injuries to dense collagenous tissues are common, but their etiology is poorly understood. The predominant hypothesis that micro-damage accumulation exceeds the rate of biological repair is missing a mechanistic explanation. Here, we used collagen hybridizing peptides to measure collagen molecular damage during tendon cyclic fatigue loading and computational simulations to identify potential explanations for our findings. Our results revealed that triple-helical collagen denaturation accumulates with increasing cycles of fatigue loading, and damage is correlated with creep strain independent of the cyclic strain rate. Finite-element simulations demonstrated that biphasic fluid flow is a possible fascicle-level mechanism to explain the rate dependence of the number of cycles and time to failure. Molecular dynamics simulations demonstrated that triple-helical unfolding is rate dependent, revealing rate-dependent mechanisms at multiple length scales in the tissue. The accumulation of collagen molecular denaturation during cyclic loading provides a long-sought "micro-damage" mechanism for the development of overuse injuries.
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http://dx.doi.org/10.1126/sciadv.aba2795 | DOI Listing |
Pathol Res Pract
September 2025
Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China. Electronic address:
Background: Dermal clear cell sarcoma (DCCS) is a rare malignant mesenchymal neoplasm. Owing to the overlaps in its morphological and immunophenotypic profiles with a broad spectrum of tumors exhibiting melanocytic differentiation, it is frequently misdiagnosed as other tumor entities in clinical practice. By systematically analyzing the clinicopathological characteristics, immunophenotypic features, and molecular biological properties of DCCS, this study intends to further enhance pathologists' understanding of this disease and provide a valuable reference for its accurate diagnosis.
View Article and Find Full Text PDFSci Adv
September 2025
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Integrins bind ligands between their alpha (α) and beta (β) subunits and transmit signals through conformational changes. Early in chordate evolution, some α subunits acquired an "inserted" (I) domain that expanded integrin's ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo-electron microscopy structures of apo and ligand-bound states of the I domain-containing αEβ integrin and the I domain-lacking αβ integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Orthopedic Surgery, Center for Shoulder and Elbow Surgery, Konkuk University School of Medicine, Seoul, Korea.
Purpose: We aimed to compare the effects of atelocollagen (AC) and individual growth factors on the expression of key molecular markers associated with tendon healing.
Methods: C2C12 myoblasts were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 5% fetal bovine serum (FBS) and treated with 1 nM or 10 nM of Atelocollagen (AC), bone morphogenetic protein-2 (BMP-2), transforming growth factor-beta 1 (TGF-β1), insulin-like growth factor-1 (IGF-1), or vascular endothelial growth factor (VEGF) for 5 days. After 5 days of treatment, cells were harvested from the culture medium, and Western blot analysis was performed to quantify the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), Collagen type I (Col I), Collagen type Ⅲ (Col Ⅲ), and Tenascin C (TnC).
Biochem Biophys Rep
December 2025
Division of Breast Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
Purpose: This study aimed to conduct functional proteomics across breast cancer subtypes with bioinformatics analyses.
Methods: Candidate proteins were identified using nanoscale liquid chromatography with tandem mass spectrometry (NanoLC-MS/MS) from core needle biopsy samples of early stage (0-III) breast cancers, followed by external validation with public domain gene-expression datasets (TCGA TARGET GTEx and TCGA BRCA).
Results: Seventeen proteins demonstrated significantly differential expression and protein-protein interaction (PPI) found the strong networks including COL2A1, COL11A1, COL6A1, COL6A2, THBS1 and LUM.
J Inflamm Res
September 2025
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Introduction: While nucleus pulposus cell (NPC) degeneration is a primary driver of intervertebral disc degeneration (IVDD), the cellular heterogeneity and molecular interactions underlying NPC degeneration remain poorly characterized. Previous studies have shown that EGFR signaling plays a significant role in NPC differentiation and collagen matrix production. Consequently, this study aims to identify the critical downstream regulatory molecule of EGFR in the process of NPC degeneration.
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