Integrative Systems Biology of the Remodeling-Permissiveness Network Applications to Osteoarthritis and Multi-Modal Therapeutic Interv

The Remodeling-Permissiveness Network (RPN) reframes chronic disease — including osteoarthritis (OA), solid malignancies, and systemic autoimmunity — as a system-level transition between stable tissue configurations rather than the product of isolated molecular pathways. Tissue permissiveness is defined as the integrated structural, immunological, and metabolic accessibility of a given tissue to immune surveillance and active remodeling, governed by nonlinear interactions across fibrinolytic balance (Plasmin-PAI-1), immune access regulation (beta-catenin, TGF-beta, PD-L1), and innate immune amplification (LL-37).