ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2017
Lysophosphatidic acid-induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty infiltration following rotator cuff tears.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Lysophosphatidic acid mediates skeletal muscle fibrosis in denervation via activation of YAP/TAZ.JCI insight · 2026Article
- Blood Flow Restriction Therapy Stimulates Intercellular Mitochondria Transfer and Improves Muscle Regeneration and Shoulder Function in a Murine Rotator Cuff Injury Model.The American journal of sports medicine · 2026Article
- Association between inflammatory proteins and rotator cuff tears: a bidirectional Mendelian randomization study.Scientific reports · 2025Article
- Emerging Roles of Lysophosphatidic Acid in Macrophages and Inflammatory Diseases.International journal of molecular sciences · 2023Review
- Article
- Electroconductivity, a regenerative engineering approach to reverse rotator cuff muscle degeneration.Regenerative biomaterials · 2023Review
- Single-cell transcriptome dynamics of the autotaxin-lysophosphatidic acid axis during muscle regeneration reveal proliferative effects in mesenchymal fibro-adipogenic progenitors.Frontiers in cell and developmental biology · 2023Article
- Clinical perspectives for repairing rotator cuff injuries with multi-tissue regenerative approaches.Journal of orthopaedic translation · 2022Review
- Roles of Oxidative Stress in Acute Tendon Injury and Degenerative Tendinopathy-A Target for Intervention.International journal of molecular sciences · 2022Review
- Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis.Scientific reports · 2022Article
- Identification of Diagnostic Biomarkers Associated with Stromal and Immune Cell Infiltration in Fatty Infiltration After Rotator Cuff Tear by Integrating Bioinformatic Analysis and Machine-Learning.International journal of general medicine · 2022Article
- Macrophage-specific RhoA knockout delays Wallerian degeneration after peripheral nerve injury in mice.Journal of neuroinflammation · 2021Article
- The linkage between inflammation and fibrosis in muscular dystrophies: The axis autotaxin-lysophosphatidic acid as a new therapeutic target?Journal of cell communication and signaling · 2021Review
- Does the Interaction between Local and Systemic Inflammation Provide a Link from Psychology and Lifestyle to Tissue Health in Musculoskeletal Conditions?International journal of molecular sciences · 2021Review
- Rotator cuff tear degeneration and the role of fibro-adipogenic progenitors.Annals of the New York Academy of Sciences · 2021Review
- Engineering Musculoskeletal Grafts for Multi-Tissue Unit Repair: Lessons From Developmental Biology and Wound Healing.Frontiers in physiology · 2021Review
- Dual Role of Lysophosphatidic Acid Receptor 2 (LPAFrontiers in cellular neuroscience · 2021Article
- Oral Ibuprofen Interferes with Cellular Healing Responses in a Murine Model of Achilles Tendinopathy.Journal of musculoskeletal disorders and treatment · 2018Article
- The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears.Tissue engineering. Part B, Reviews · 2017Article
- Quantitative analysis of immune cell subset infiltration of supraspinatus muscle after severe rotator cuff injury.Regenerative engineering and translational medicine · 2017Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Previous studies have suggested that macrophage-mediated chronic inflammation is involved in the development of rotator cuff muscle atrophy and degeneration following massive tendon tears. Increased RhoA signaling has been reported in chronic muscle degeneration, such as muscular dystrophy. However, the role of RhoA signaling in macrophage infiltration and rotator muscle degeneration remains unknown. Using a previously established rat model of massive rotator cuff tears, we found RhoA signaling is upregulated in rotator cuff muscle following a massive tendon-nerve injury. This increase in RhoA expression is greatly potentiated by the administration of a potent RhoA activator, lysophosphatidic acid (LPA), and is accompanied by increased TNFα and TGF-β1 expression in rotator cuff muscle. Boosting RhoA signaling with LPA significantly worsened rotator cuff muscle atrophy, fibrosis, and fatty infiltration, accompanied with massive monocytic infiltration of rotator cuff muscles. Co-staining of RhoA and the tissue macrophage marker CD68 showed that CD68+ tissue macrophages are the dominant cell source of increased RhoA signaling in rotator cuff muscles after tendon tears. Taken together, our findings suggest that LPA-mediated RhoA signaling in injured muscle worsens the outcomes of atrophy, fibrosis, and fatty infiltration by increasing macrophage infiltraion in rotator cuff muscle. Clinically, inhibiting RhoA signaling may represent a future direction for developing new treatments to improve muscle quality following massive rotator cuff tears. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1539-1547, 2017.
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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 Socratic graph.