Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria; Corresponding author at: Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria.
Gabriel Spitzer
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria
Patrick Langthaler
Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, Affiliated member of the European Reference Network EpiCARE, Austria; Department of Mathematics, Paris Lodron University of Salzburg, Salzburg, Austria; Team Biostatistics and Big Medical Data, IDA Lab Salzburg, Paracelsus Medical University, Salzburg, Austria
Dominika Jakubecova
Institute of Experimental Neuroregeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria
Barbara Klein
Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria
Nadja Weissenbacher
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria
Andrea Wagner
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria
Renate Gehwolf
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria
Eugen Trinka
Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, Affiliated member of the European Reference Network EpiCARE, Austria; Department of Public Health, Health Services Research and Health Technology Assessment, UMIT–University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria; Neuroscience Institute, Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience Salzburg, Austria
Bernhard Iglseder
Department of Geriatric Medicine, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
Bernhard Paulweber
Department of Internal Medicine, St. Johanns University Hospital, Paracelsus Medical University, Salzburg, Austria
Ludwig Aigner
Austrian Cluster for Tissue Regeneration, Vienna, Austria; Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria
Sebastien Couillard-Després
Austrian Cluster for Tissue Regeneration, Vienna, Austria; Institute of Experimental Neuroregeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria
Richard Weiss
Department of Biosciences, Paris Lodron University of Salzburg, Salzburg, Austria
Herbert Tempfer
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria
Andreas Traweger
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, Strubergasse 22, Salzburg 5020, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria
Summary: Background: Treatment of degenerating tendons still presents a major challenge, since the aetiology of tendinopathies remains poorly understood. Besides mechanical overuse, further known predisposing factors include rheumatoid arthritis, diabetes, obesity or smoking all of which combine with a systemic inflammation. Methods: To determine whether the systemic inflammation accompanying these conditions contributes to the onset of tendinopathy, we studied the effect of a systemic inflammation induced by an allergic episode on tendon properties. To this end, we induced an allergic response in mice by exposing them to a timothy grass pollen allergen and subsequently analysed both their flexor and Achilles tendons. Additionally, we analysed data from a health survey comprising data from more than 10.000 persons for an association between the occurrence of an allergy and tendinopathy. Findings: Biomechanical testing and histological analysis revealed that tendons from allergic mice not only showed a significant reduction of both elastic modulus and tensile stress, but also alterations of the tendon matrix. Moreover, treatment of 3D tendon-like constructs with sera from allergic mice resulted in a matrix-remodelling expression profile and the expression of macrophage-associated markers and matrix metalloproteinase 2 (MMP2) was increased in allergic Achilles tendons. Data from the human health study revealed that persons suffering from an allergy have an increased propensity to develop a tendinopathy. Interpretation: Our study demonstrates that the presence of a systemic inflammation accompanying an allergic condition negatively impacts on tendon structure and function. Funding: This study was financially supported by the Fund for the Advancement of Scientific Research at Paracelsus Medical University (PMU-FFF E-15/22/115-LEK), by the Land Salzburg, the Salzburger Landeskliniken (SALK, the Health Care Provider of the University Hospitals Landeskrankenhaus and Christian Doppler Klinik), the Paracelsus Medical University, Salzburg and by unrestricted grants from Bayer, AstraZeneca, Sanofi-Aventis, Boehringer-Ingelheim.
