Sex, but not age and bone mass index positively impact on the development of osteochondral micro-defects and the accompanying cellular alterations during osteoarthritis progression

Angelos Kaspiris; Efstathios Chronopoulos; Elias Vasiliadis; Lubna Khaldi; Dimitra Melissaridou; Ilias D Iliopoulos; Olga D Savvidou

doi:10.1002/cdt3.16

Sex, but not age and bone mass index positively impact on the development of osteochondral micro-defects and the accompanying cellular alterations during osteoarthritis progression

Chronic Dis Transl Med. 2022 Mar 29;8(1):41-50. doi: 10.1002/cdt3.16. eCollection 2022 Mar.

Authors

Angelos Kaspiris¹, Efstathios Chronopoulos², Elias Vasiliadis³, Lubna Khaldi⁴, Dimitra Melissaridou⁵, Ilias D Iliopoulos⁶, Olga D Savvidou⁵

Affiliations

¹ Laboratory of Molecular Pharmacology, Division for Orthopaedic Research, School of Health Sciences University of Patras Patras Greece.
² Second Department of Orthopaedic Surgery, School of Medicine National and Kapodistrian University of Athens, "Konstantopoulio" General Hospital Athens Greece.
³ Third Department of Orthopaedic Surgery "KAT" General Hospital and Medical School University of Athens Athens Greece.
⁴ Department of Pathology "Agios Savvas" Athens Cancer Hospital-NHS Athens Greece.
⁵ First Department of Orthopaedic Surgery, School of Medicine National and Kapodistrian University of Athens, "ATTIKON" University General Hospital Athens Greece.
⁶ Department of Orthopaedic Surgery, "Rion" University Hospital and Medical School, School of Health Sciences University of Patras Patras Greece.

PMID: 35620158
PMCID: PMC9128565
DOI: 10.1002/cdt3.16

Abstract

Background: Osteoarthritis (ΟΑ) is characterized by cartilage breakdown and subchondral sclerosis. Micro-fractures of the calcified tissues have been, also, detected, but their exact role has not been elucidated yet. This study was to examine the frequency of cracks during OA progression and to correlate them with the underlying cellular modifications and matrix metalloproteinase-2 (MMP-2) expression using histological/immunohistological methods.

Methods: Overall, 20 patients and 3 controls (9 specimens per patient), aged 60-89 years, diagnosed with hip/knee OA were included. The development of cracks was examined in 138 sections, whereas the expression of MMP-2 was examined in 69 additional sections.

Results: Based on Mankin score, three groups of OA severity were analyzed: Group I (mild) was constituted of sections with score 1-5 while Groups II (moderate) and III (severe) with score 6-7 and greater or equal to 8, respectively. Demographic characteristics did not reveal any association between the number of microdefects and age or body mass index (BMI). Cartilage micro-cracks were increased during moderate and severe OA, while bone cracks were increased during mild and severe OA. In knee OA, cartilage cracks were not correlated with Mankin score, whereas in hip OA they appeared association with severity score. Bone cracks were positively correlated with matrix apoptotic osteocytes and osteoblastic cells, but not with osteoclasts. MMP-2 immunostaining was increasing by OA severity in the osteochondral unit. Similarly, MMP-2 was expressed on the microcracks' wall mainly in Group III.

Conclusion: Our data displayed that bone cracks during primary OA stages, represent an early adaptative mechanism aiming to maintain cartilage integrity. Accumulation of bone defects and concomitant increase of apoptotic osteocytes activated an abnormal remodeling due to osteoblastic activity, in which MMP-2 played a pivotal role, leading to subchondral sclerosis promoting further osteochondral deformities.

Keywords: demographic characteristics; matrix metalloproteinase‐2; micro‐cracks; osteoarthritis.