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

doi:10.1016/j.pathophys.2015.06.001

Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity

Pathophysiology. 2015 Sep;22(3):143-51. doi: 10.1016/j.pathophys.2015.06.001. Epub 2015 Jun 23.

Authors

Angelos Kaspiris¹, Lubna Khaldi², Efstathios Chronopoulos², Elias Vasiliadis³, Theodoros B Grivas⁴, Ioannis Kouvaras³, Spyridon Dagkas³, Evangelia Papadimitriou⁵

Affiliations

¹ Department of Trauma and Orthopaedics, Thriasio General Hospital of Attica - NHS, G. Gennimata av., Athens, Magoula 19600, Greece; Laboratory for Research of the Musculoskeletal System, School of Medicine, University of Athens, Attica, Greece; Laboratory of Molecular Pharmacology, School of Health Sciences, University of Patras, Greece. Electronic address: angkaspiris@hotmail.com.
² Laboratory for Research of the Musculoskeletal System, School of Medicine, University of Athens, Attica, Greece.
³ Department of Trauma and Orthopaedics, Thriasio General Hospital of Attica - NHS, G. Gennimata av., Athens, Magoula 19600, Greece.
⁴ Department of Trauma and Orthopaedics, Tzanio General Hospital of Piraeus - NHS, Piraeus 18536, Attica, Greece.
⁵ Laboratory of Molecular Pharmacology, School of Health Sciences, University of Patras, Greece.

PMID: 26126948
DOI: 10.1016/j.pathophys.2015.06.001

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.

Keywords: BMI; Immunohistochemistry; MMP-12; Osteoarthritis.