Volume 22, Issue 3, Pages 143-151 (September 2015) Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity  Angelos Kaspiris, Lubna Khaldi, Efstathios Chronopoulos, Elias Vasiliadis, Theodoros B. Grivas, Ioannis Kouvaras, Spyridon Dagkas, Evangelia Papadimitriou  Pathophysiology  Volume 22, Issue 3, Pages 143-151 (September 2015) DOI: 10.1016/j.pathophys.2015.06.001 Copyright © 2015 Elsevier B.V. Terms and Conditions

Fig. 1 Representative histological characteristics of the studied groups. (A) In slice of Mankin score 3 (group I) a diffuse hypercellularity of the cartilage was observed with absence of pannus or surface irregularities. (B) In slice of Mankin score 5 (group II) clefts to the deeper cartilage zones (black arrows) and chondrocytes cloning (red arrows) were noted. (C) Pannus, surface discontinuity, cartilage erosions (black arrows) fibrocartilage and the characteristic hypocellularity (red arrows), were noted in slice of group III (Mankin score 7). (D) Pannus, surface erosions and vertical fissures into the calcified zone (black arrows) as well as fibrocartilage and hypocellularity, were detected in section of group IV (Mankin score 9). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) Pathophysiology 2015 22, 143-151DOI: (10.1016/j.pathophys.2015.06.001) Copyright © 2015 Elsevier B.V. Terms and Conditions

Fig. 2 Statistical analysis of MMP-12 immunoexpression in hip (A) and knee (B) OA tissues. Bars are expressed as mean±SEM. P values determined by Kruskal–Wallis test. *p<0.05 as compared with controls, **p<0.01 as compared with controls. Pathophysiology 2015 22, 143-151DOI: (10.1016/j.pathophys.2015.06.001) Copyright © 2015 Elsevier B.V. Terms and Conditions

Fig. 3 Cartilage and subchondral bone without OA changes in a control negative for MMP-12. Pathophysiology 2015 22, 143-151DOI: (10.1016/j.pathophys.2015.06.001) Copyright © 2015 Elsevier B.V. Terms and Conditions

Fig. 4 (A) Cartilage matrix with limited positive expression of MMP-12 (black arrows) in patient with Mankin score 2. (B) MMP-12 is expressed in the fibrocartilage and pannus of patient with Mankin score 7. (C and D) Osteoblast-like cells (black arrows) and osteocytes (red arrows) of the subchondral bone express MMP-12 in a patient with severe OA changes (Mankin 8 and 9, respectively). Note the intense immunostaining of the underlying disorganized cartilage (red arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) Pathophysiology 2015 22, 143-151DOI: (10.1016/j.pathophys.2015.06.001) Copyright © 2015 Elsevier B.V. Terms and Conditions

Fig. 5 (A) The matrix around osteoblasts (black arrows) and osteoclasts (red arrows) is immunostained for MMP-12 in patient with Mankin score 5. Note the multinuclear osteoclasts into the characteristic Howship's lacunae. (B) Cytoplasmic expression of MMP-12 in the osteocytes (black arrows) of section with Mankin score 7. (C) The osteoblastic-like cells (black arrows) of subchondral bone and bone cysts express limited MMP-12 in patient with Mankin score 7. (D) Cytoplasmic tracing of MMP-12 in clusters of chondrocytes (black arrows) in patient with Mankin score 8.MMP-12 is detected in the matrix of the adjacent osteoblast-like cells (red arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) Pathophysiology 2015 22, 143-151DOI: (10.1016/j.pathophys.2015.06.001) Copyright © 2015 Elsevier B.V. Terms and Conditions

Fig. 6 (A) The matrix around chondroblasts (black arrows) and chondrocytes (red arrows) is immunostained for MMP-12 in patient with Mankin score 10. Note the characteristic ovoid morphology of chondroblasts. (B) Cytoplasmic expression of MMP-12 in osteocytes (black arrows) from a slice with Mankin score 6. (C) Slice from patient with Mankin score 5. Note significant expression of MMP-12 by the osteoblast-like cells (black arrows). (D) MMP-12 expression of the matrix next to osteoclast (black arrows) in patient with moderate OA changes (Mankin 6). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) Pathophysiology 2015 22, 143-151DOI: (10.1016/j.pathophys.2015.06.001) Copyright © 2015 Elsevier B.V. Terms and Conditions

Fig. 7 The wall osteoblast (black arrows) of subchondral cysts strongly express MMP-12 in slices with Mankin score 6. Pathophysiology 2015 22, 143-151DOI: (10.1016/j.pathophys.2015.06.001) Copyright © 2015 Elsevier B.V. Terms and Conditions