Extracellular Matrix Degradation and Tissue Remodeling in Periprosthetic Loosening and Osteolysis: Focus on Matrix Metalloproteinases, Their Endogenous Tissue Inhibitors, and the Proteasome

Table 1

Matrix metalloproteinases (MMPs) in periprosthetic microenvironment (expression and/or activity: ↑ with bold data: high; ↑ without bold data: moderate).

MMPs		Substrates	Expression and/or activity in periprosthetic microenvironment [References]
Collagenases
Contain hemopexin domain and peptide linking with catalytic domain	MMP-1  (interstitial collagenase; collagenase 1); MMP-8  (neutrophil collagenase; collagenase 2); MMP-13  (collagenase 3)	Collagen type I, III, V, VII, VIII, X, gelatin, IL-1β, MMP-2, -9, fibronectin	↑MMP-1  [39, 58, 70, 72, 80, 82, 90]; ↑MMP-8 [70]; ↑MMP-13  [70, 82, 89]
Gelatinases
High substrate specificity to native collagen and gelatin	MMP-2  (gelatinase A; 72 kDa metalloproteinase); MMP-9  (gelatinase B; 92 kDa metalloproteinase)	Collagen type IV, V, VII, X, proteoglycans, gelatin, elastin, laminin	↑MMP-2  [58, 70, 73, 74, 76, 77, 80, 90]; ↑MMP-9  [58, 70, 76, 77, 80, 90, 91]
Stromelysins
Metalloproteinases of stroma	MMP-3  (stromelysin 1); MMP-10  (stromelysin 2); MMP-11  (stromelysin 3)	Proteoglycans, fibronectin, laminin, elastin, gelatin, plasminogen, vitronectin, fibrinogen, fibrin, collagen type III, IV, V, antithrombin III, MMP-1, -2, -8, -9, -13	↑MMP-3 [58, 70, 74, 80]; ↑MMP-10  [70]; ↑MMP-11 [70]
Matrilysins
The smallest among MMPs, lack of hemopexin domain	MMP-7  (matrilysin, metalloendopeptidase); MMP-26  (matrilysin-2, endometase)	Collagen type IV, proteoglycans, glycoproteins, gelatin	↑MMP-7 [70]
Membrane-type MMPs
(A)  Transmembrane-type MMPs	MMP-14  (MT1-MMP); MMP-15  (MT2-MMP); MMP-16  (MT3-MMP); MMP-24  (MT5-MMP)	Collagen type I, II, III, gelatin, elastin, laminin, fibronectin, fibrin, proteoglycans, proMMP-2, proMMP-13	↑MMP-14  [70, 73]; ↑MMP-15 [70]; ↑MMP-16 [70]
(B) GPI-anchored MMPs	MMP-17  (MT4-MMP); MMP-25  (MT6-MMP)		↑MMP-17 [70]
Other MMPs
MMPs that are not categorized in any of the previous groups	MMP-12  (macrophage metalloelastase); MMP-19; MMP-20  (enamelysin); MMP-21,  MMP-23; MMP-27,  MMP-28		↑MMP-12  [70]; ↑MMP-19 [70]