Zinc- and calcium-dependent endopeptidases that degrade extracellular matrix (ECM) components including collagen, gelatin, elastin, proteoglycans, and basement membrane proteins. MMPs are essential for wound healing, tissue remodeling, angiogenesis, and immune cell migration, but excessive or unregulated activity drives tissue destruction in chronic inflammation.
MMPs are secreted as inactive pro-enzymes (zymogens) requiring proteolytic cleavage or conformational change for activation. They cleave ECM proteins at specific sites: collagenases (MMP-1, MMP-8, MMP-13) cleave fibrillar collagens; gelatinases (MMP-2, MMP-9) degrade denatured collagen and basement membrane; stromelysins (MMP-3, MMP-10) have broad substrate specificity. MMPs require zinc at the catalytic site and calcium for structural stability. They are produced by neutrophils, macrophages, fibroblasts, and mesenchymal cells during: (1) Wound healing—clearing damaged matrix and creating pathways for new cells, (2) Angiogenesis—degrading basement membrane for vessel sprouting, (3) Immune cell migration—creating paths through ECM. Activity is controlled by TIMPs (tissue inhibitors of metalloproteinases). Excessive MMP activity occurs in chronic inflammation, cancer invasion, arthritis, periodontal disease.
MMPs are essential for healing but destructive when dysregulated. In wound healing, MMPs clear damaged tissue and allow fibroblast and endothelial cell migration—deficiency impairs healing. However, chronic elevation (from persistent inflammation, smoking, diabetes, nutrient deficiency) causes: (1) Cartilage destruction in osteoarthritis, (2) Periodontal bone loss, (3) Skin aging (collagen degradation), (4) Cancer metastasis (basement membrane degradation). cPNI interventions: (1) Ensure cofactors (zinc, selenium, manganese) for proper MMP function during healing, (2) Reduce chronic inflammation to prevent excessive MMP activation, (3) Support TIMP production via nutrients and resolution pathways.