Pathological similarities between degenerative enthesopathy and rheumatic enthesitis: the role of ECM stiffness and Wolff's Law-based mechanical stimulation as a therapeutic strategy.

Degenerative enthesopathy and rheumatic enthesitis have traditionally been regarded as distinct disorders driven by mechanical overload and immune dysregulation, respectively. However, increasing evidence suggests that the mechanobiological links between these conditions have been underappreciated. In particular, pathological stiffening of the extracellular matrix (ECM) at the enthesis has emerged as a potential common mechanism connecting cumulative mechanical loading, chronic low-grade inflammation, and dysregulated mechanotransduction. This review synthesizes current biomechanical and immunological evidence linking ECM rigidity to fibrocartilage metaplasia, bone marrow edema, and pathological neo-osteogenesis. Histopathological similarities between degenerative and inflammatory phenotypes, including subperiosteal fibrosis, advancing mineralization fronts, and immune-cell trafficking through transcortical vessels (TCVs), further support the concept of a shared disease continuum. ECM stiffness may represent a shared mechanobiological feature contributing to structural degeneration, chronic inflammation, and aberrant ossification in both conditions. We further examine the therapeutic potential of Wolff's Law-based mechanical stimulation strategies, including dry needling, vibration therapy, and targeted mechanical stimulation of periosteal and entheseal regions. These interventions engage mechanosensitive pathways that may restore matrix compliance, improve microvascular perfusion, and modulate inflammatory activity within the enthesis microenvironment. Taken together, the available evidence indicates that ECM stiffness is not only a marker of disease progression but also a plausible therapeutic target. This perspective may inform future stiffness-oriented treatment strategies, including bio-electric stimulation-based approaches, for restoring enthesis homeostasis in both degenerative and rheumatic disorders.