At the Cell–Matrix Interface: Inflammatory Signaling and the Mechanobiology of Tendinopathy
Abstract:
Tendinopathy is a common and often persistent musculoskeletal disorder characterized by extracellular-matrix disorganization, altered tissue mechanics, and chronic inflammatory signaling. Yet the mechanisms linking changes in the extracellular matrix to sustained cellular dysfunction remain incompletely understood. This seminar will examine how nuclear factor kappa B (NF-κB) signaling contributes to tendon degeneration and repair, with emphasis on the reciprocal relationship between tendon cells and their extracellular matrix. Using biomechanical, cellular, and preclinical models, our work shows that dysregulated NF-κB activity can drive chronic tendon pathology and impair healing, while targeted modulation of this pathway may improve tendon-to-bone repair. I will also discuss emerging evidence that matrix composition and mechanics shape fibroblast inflammatory responses, metabolism, and mechanosensing. Together, these studies position the cell–matrix interface as a critical regulator of tendinopathy and a promising target for therapeutic development..
Bio:
Adam C. Abraham, PhD, is an Assistant Professor of Orthopaedic Surgery at the University of Michigan. Trained in mechanical engineering, biomedical engineering, musculoskeletal biology, and immunology, Dr. Abraham studies how mechanical loading, extracellular-matrix properties, and inflammatory signaling interact to regulate connective-tissue health and disease. His laboratory focuses on tendon mechanobiology and pathophysiology, particularly the role of cell–extracellular matrix interactions in controlling fibroblast behavior and chronic inflammation. Dr. Abraham’s research has helped establish NF-κB signaling as a mechanistic driver and potential therapeutic target in tendinopathy and tendon-to-bone healing. His current National Institutes of Health-funded work examines how the extracellular matrix regulates inflammatory signaling in tendon. By integrating multiscale biomechanics, engineered tissue models, and preclinical disease models, his research seeks to identify mechanisms that can be translated into improved treatments for tendon injury and degeneration.