Mechanical loading is an important factor in musculoskeletal health and disease. Tendons and ligaments require physiological levels of mechanical loading to develop and maintain their tissue architecture, a process that is achieved at the cellular level through mechanotransduction-mediated fine-tuning of the extracellular matrix by tendon and ligament stromal cells. Pathological levels of force represent a biological (mechanical) stress that elicits an immune system-mediated tissue repair pathway in tendons and ligaments.

The biomechanics and mechanobiology of tendons and ligaments form the basis for understanding how such tissues sense and respond to mechanical force, and the anatomical extent of several mechanical stress-related disorders in tendons and ligaments overlaps with that of chronic inflammatory arthritis in joints. The role of mechanical stress in ‘overuse’ injuries, such as tendinopathy, has long been known, but mechanical stress is now also emerging as a possible trigger for some forms of chronic inflammatory arthritis, including spondyloarthritis and rheumatoid arthritis.

Thus, seemingly diverse diseases of the musculoskeletal system might have similar mechanisms of immunopathogenesis owing to conserved responses to mechanical stress.

Key points

• Mechanical loading is a biological stressor that elicits a homeostatic response to ensure the health and survival of the cells and/or tissues it is applied to.
• Tissues that encounter high amounts of mechanical stress are prone to damage, especially the tendon and ligament entheses.
• The immune system is crucial in responding to and orchestrating the repair of damaged tendons and ligaments.
• Mechanical loading is a well-defined factor in the immunopathology of tendon and ligament disorders such as tendinopathy.
• Mechanical loading is associated with the onset of chronic inflammatory arthritis, including spondyloarthritis (SpA) and rheumatoid arthritis (RA).
• Microdamage associated with mechanical loading potentially focuses systemic autoimmune disease on the joint in the initiating phases of SpA and RA.

Reference: Gracey, E., Burssens, A., Cambré, I. et al. Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis. Nat Rev Rheumatol 16, 193–207 (2020). https://doi.org/10.1038/s41584-019-0364-x