journal article·2026-02Open access

Increased Blood Flow and Tendon Swelling Precedes Vascular Expansion and Tissue Matrix Changes In Early Human Tendinopathy: A Potential Window for Superior Treatment Response

Max F. R. Merkel, Nikolaj M. Malmgaard‐Clausen, Marius Lendal, Hartwig R. Siebner, René B. Svensson, Stephanie G. Dakin, Marcus Krüger, Luisa Schmidt, Jakob Agergaard, Ching‐Yan Chloé Yeung, S. Peter Magnusson, Michael Kjaer

Advanced Science· Volume 13· Issue 12

Abstract

Abstract Tendinopathy represents a major musculoskeletal health problem, yet its pathogenesis remains poorly understood. Tendinopathy development is studied in humans with early (< 3 months of symptoms, n = 14) (ET) or chronic (> 3 months, n = 16) (CT) patellar tendinopathy and in healthy subjects ( n = 15) (CTRL). Pain increases, and function declines with tendinopathy duration and correlated with tendon size (3T and 7T MRI). Tendon blood flow (Doppler ultrasonography) increases gradually in ET and CT, while peritendinous blood flow only rose in CT. Microscopy‐based mapping (immunofluorescence microscopy and Cell DIVE) of vasculature shows marked changes in CT only, indicating flow increases in existing vessels early in tendinopathy, whereas angiogenesis is a late phenomenon. Cell DIVE indicates perivascular cell recruitment and potential lymphatic expansion in tendinopathy. Further, proteomics reveals that most matrix regulation occurs late in tendinopathy. Data from a previous study from the lab demonstrate faster treatment effect in tendinopathy with shorter symptom duration, supporting that early tissue changes may be more receptive to treatment. It is concluded that early tendinopathy is dominated by pain correlating with tendon swelling and hyperperfusion, whereas chronic tendinopathy is characterized by neovascularization and matrisome changes. These findings suggest that targeting early tissue changes can lead to superior treatment effects in tendinopathy.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Tendon Structure and Treatment · Shoulder Injury and Treatment · Sports injuries and prevention

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Sports Medicine Copenhagen Department of Orthopedic Surgery Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen 2400 Denmark

Department of Clinical Medicine University of Copenhagen Copenhagen 2200 Denmark

Danish Research Centre for Magnetic Resonance Department of Radiology and Nuclear Medicine Copenhagen University Hospital‐Amager and Hvidovre Copenhagen 2650 Denmark

Department of Neurology Copenhagen University Hospital Bispebjerg and Frederiksberg Copenhagen 2400 Denmark

Center for Fast Ultrasound Imaging Department of Health Technology Technical University of Denmark Lyngby 2800 Denmark

Botnar Institute for Musculoskeletal Sciences Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford Oxford OX3 7LD UK

NIHR Oxford Biomedical Research Unit Botnar Research Centre University of Oxford Oxford OX3 7LD UK

Institute for Genetics Cologne Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) University of Cologne 50931 Cologne Germany

Center for Molecular Medicine (CMMC) University of Cologne 50931 Cologne Germany

Novo Nordisk Foundation Center for Protein Research Department of Cellular and Molecular Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen 2200 Denmark

Funding

Danmarks Frie Forskningsfond · Novo Nordisk Fonden · Versus Arthritis · Lundbeck Foundation · Innovationsfonden

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