SPARCling Matrix

The essential role of the matricellular protein SPARC in tendon disease and healing

Injuries and pathological changes in tendons represent a major challenge for orthopedics, especially as the number of these diseases increases dramatically with age and injured tendons heal poorly. In addition to inflammatory processes, changes in tendon structure (extracellular matrix) and tendon cells are central for the development and progression of tendon diseases, the so-called tendinopathies.

Recent studies in various other tissues show, that alterations in the extracellular matrix also impacts on the metabolic landscape of the tissue, resulting in poor healing outcomes and scar formation. Initial results suggest that similar processes contribute to the limited healing of tendons. However, the underlying mechanisms are still poorly understood.

One goal of the project is to investigate these processes using comprehensive molecular and cell biological methods. These investigations will be performed using a genetically modified mouse model lacking the tendon-relevant protein SPARC (Secreted Protein Acidic and Rich in Cysteine). These animals have severely impaired tendons showing characteristics comparable to tendinopathy in humans.

In the second project goal, we aim to develop a digital platform for automated and objective evaluation of tissue sections based on three typical structural features of diseased tendons. To this end, the students of HTBLuVA Salzburg (Major: biomedicine and health technology), together with the cooperation partners, will develop software tools using AI-based techniques (e.g. "deep learning" and segmentation methods) and integrate them into a user-friendly app. In doing so, the students will learn first-hand about both the technical and biological backgrounds of the emerging AI-based digital pathology.

Our own preliminary results indicate a therapeutic effect of SPARC for injured tendons. In the third project aim a well-established tendon defect model will be employed to assess the efficacy of a local administration of SPARC to improve tendon healing. For analysis of the repair tissue we will make use of the digital platform established in goal 2.

Elucidating the molecular and cellular factors driving tendinopathy and the development of an automated scoring tool will help us to better understand and characterize the underlying processes causing tendinopathic degenerations. The potential beneficial effect of SPARC on tendon healing potentially provides new possibilities to treat tendon injuries.