2015•PathophysiologyOpen access

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 S. Vasiliadis, Theodoros B Grivas, Ioannis Kouvaras, S. Dagkas, Εvangelia Papadimitriou

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Abstract

BACKGROUND: Metalloproteinase 12 (MMP-12) is induced in chondrocytes during fetal development and malignant transformation. OBJECTIVES: The aim of our study is to examine the expression of MMP-12 in the cartilage and the subchondral bone of patients with osteoarthritis (OA) and to correlate its expression with disease severity and anthropometric characteristics. METHODS: Overall, 60 sections from 20 patients with idiopathic OA, were examined for the immunolocalization of MMP-12. As controls, we used the femoral heads of 4 patients treated with seniarthroplasty after fracture. Demographic characteristics and Body Mass Index (BMI) were calculated for all subjects. RESULTS: Specimens were divided into four groups based on the Mankin histological severity score. The immunohistochemical study showed MMP-12 expression in the cartilage and subchonral bone of OA patients, while there was no expression in normal controls. At the moderate OA changes (Mankin score: 6-7), MMP-12 was detected mainly at the matrix of fibrocartilage tissue. During disease progression, MMP-12 was expressed at the sides of the cartilage and bone erosion and in the bone cysts. Furthermore, it was traced in the osteocytes of the subchondral bone. Osteoblast-like cells and bone lining cells express MMP-12 during the stage of severe OA (Mankin: ≥8). Osteoclasts expressing MMP-12 were also detected in the group of severe OA. Interestingly, MMP-12 expression was positively correlated with the age and the BMI of OA patients. CONCLUSION: The increased expression of MMP-12 in the bone-cartilage unit of OA patients suggests a possible role in OA pathogenesis and progression. LEVEL OF EVIDENCE: III, prospective comparative study.

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BACKGROUND: Metalloproteinase 12 (MMP-12) is induced in chondrocytes during fetal development and malignant transformation. OBJECTIVES: The aim of our study is to examine the expression of MMP-12 in the cartilage and the subchondral bone of patients with osteoarthritis (OA) and to correlate its expression with disease severity and anthropometric characteristics. METHODS: Overall, 60 sections from 20 patients with idiopathic OA, were examined for the immunolocalization of MMP-12. As controls, we used the femoral heads of 4 patients treated with seniarthroplasty after fracture. Demographic characteristics and Body Mass Index (BMI) were calculated for all subjects. RESULTS: Specimens were divided into four groups based on the Mankin histological severity score. The immunohistochemical study showed MMP-12 expression in the cartilage and subchonral bone of OA patients, while there was no expression in normal controls. At the moderate OA changes (Mankin score: 6-7), MMP-12 was detected mainly at the matrix of fibrocartilage tissue. During disease progression, MMP-12 was expressed at the sides of the cartilage and bone erosion and in the bone cysts. Furthermore, it was traced in the osteocytes of the subchondral bone. Osteoblast-like cells and bone lining cells express MMP-12 during the stage of severe OA (Mankin: ≥8). Osteoclasts expressing MMP-12 were also detected in the group of severe OA. Interestingly, MMP-12 expression was positively correlated with the age and the BMI of OA patients. CONCLUSION: The increased expression of MMP-12 in the bone-cartilage unit of OA patients suggests a possible role in OA pathogenesis and progression. LEVEL OF EVIDENCE: III, prospective comparative study.

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Available abstract

BACKGROUND: Metalloproteinase 12 (MMP-12) is induced in chondrocytes during fetal development and malignant transformation. OBJECTIVES: The aim of our study is to examine the expression of MMP-12 in the cartilage and the subchondral bone of patients with osteoarthritis (OA) and to correlate its expression with disease severity and anthropometric characteristics. METHODS: Overall, 60 sections from 20 patients with idiopathic OA, were examined for the immunolocalization of MMP-12. As controls, we used the femoral heads of 4 patients treated with seniarthroplasty after fracture. Demographic characteristics and Body Mass Index (BMI) were calculated for all subjects. RESULTS: Specimens were divided into four groups based on the Mankin histological severity score. The immunohistochemical study showed MMP-12 expression in the cartilage and subchonral bone of OA patients, while there was no expression in normal controls. At the moderate OA changes (Mankin score: 6-7), MMP-12 was detected mainly at the matrix of fibrocartilage tissue. During disease progression, MMP-12 was expressed at the sides of the cartilage and bone erosion and in the bone cysts. Furthermore, it was traced in the osteocytes of the subchondral bone. Osteoblast-like cells and bone lining cells express MMP-12 during the stage of severe OA (Mankin: ≥8). Osteoclasts expressing MMP-12 were also detected in the group of severe OA. Interestingly, MMP-12 expression was positively correlated with the age and the BMI of OA patients. CONCLUSION: The increased expression of MMP-12 in the bone-cartilage unit of OA patients suggests a possible role in OA pathogenesis and progression. LEVEL OF EVIDENCE: III, prospective comparative study.

Key concepts: Medicine, Osteoarthritis, Matrix metalloproteinase, Macrophage, Disease, Internal medicine, Immunology, Pathology

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