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Updated: May 26, 2026
Non-Invasive Compression-Induced Anterior Cruciate Ligament (ACL) Injury and In Vivo Imaging of Protease Activity in Mice
Published on: September 29, 2023
Protein Response to ACL Injury in Humans Show Early Cartilage Remodeling and Differences by Sex
Paula A Hernandez1,2, Constance R Chu3, Chun-Yuan Huang4
1Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Anterior cruciate ligament (ACL) tears impact cartilage, with sex-specific protein changes observed. Females show distinct metabolic pathway responses compared to males after ACL injury, indicating sex influences cartilage remodeling.
Area of Science:
- Biochemistry
- Orthopedics
- Proteomics
Background:
- Anterior cruciate ligament (ACL) tears elevate the risk of posttraumatic osteoarthritis (PTOA), with females exhibiting a higher susceptibility.
- Limited research exists on sex-specific protein level changes in human cartilage following ACL injury.
- This study investigates sex-based differences in the articular cartilage proteome after an injurious event.
Purpose of the Study:
- To compare proteomic profiles of normal and injured human cartilage after ACL tears.
- To identify sex-specific protein alterations and pathway enrichment in response to cartilage injury.
- To elucidate the role of sex in the early stages of posttraumatic osteoarthritis development.
Main Methods:
- Proteomic analysis of normal and ACL-injured human cartilage from the intercondylar area.
- Comparison of protein expression between sexes (Injured Male vs. Normal Male; Injured Female vs. Normal Female).
- Pathway enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases; Matrisome AnalyzeR for extracellular matrix proteins.
Main Results:
- Over 2,188 proteins were identified, with 1,121 upregulated and 23 downregulated proteins shared between sexes in injured cartilage.
- Early cartilage remodeling was evident in both sexes, with similar responses in extracellular matrix (ECM) proteins and enriched pathways.
- Significant sex-specific differences were found in over 240 proteins, particularly in inflammation, ECM-related, and metabolic pathways. Males showed enrichment in ECM-receptor interactions, while females showed enrichment in citrate cycle, fatty acid degradation, and metabolism pathways.
Conclusions:
- Articular cartilage undergoes early remodeling post-ACL injury, even without direct physical impact.
- Sex-specific differences in inflammation, metabolic pathways, and ECM synthesis are present after ACL injury.
- These findings highlight the differential biological responses to injury based on sex, contributing to varied PTOA risk.
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