Affiliations 

  • 1 Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS10 5NB, UK
  • 2 Department of Biomedical Science, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia
  • 3 Department of Trauma and Orthopaedics, Bristol Royal Infirmary, University Hospitals Bristol and NHS Foundation Trust, Bristol BS2 8HW, UK
  • 4 Department of Oncology and Metabolism and Insigneo Institute for In Silico Medicine, University of Sheffield, Sheffield S1 3JD, UK
  • 5 Bristol Medical School, University of Bristol, Bristol BS8 1UD, UK
Biomedicines, 2021 Nov 01;9(11).
PMID: 34829822 DOI: 10.3390/biomedicines9111593

Abstract

BACKGROUND: The purpose of this study was to investigate the relationship between the expression of key degradative enzymes by chondrocytes and the microarchitectural and mineral properties of subchondral bone across different stages of cartilage degradation in human hip osteoarthritis (OA).

METHODS: Osteochondral samples at different stages of cartilage degradation were collected from 16 femoral heads with OA. Osteochondral samples with normal cartilage were collected from seven femoral heads with osteoporosis. Microcomputed tomography was used for the investigation of subchondral bone microarchitecture and mineral densities. Immunohistochemistry was used to study the expression and distribution of MMP13 and ADAMTS4 in cartilage.

RESULTS: The microarchitecture and mineral properties of the subchondral plate and trabecular bone in OA varied with the severity of the degradation of the overlying cartilage. Chondrocytes expressing MMP13 and ADAMTS4 are mainly located in the upper zone(s) of cartilage regardless of the histopathological grades. The zonal expression of these enzymes in OA (i.e., the percentage of positive cells in the superficial, middle, and deep zones), rather than their overall expression (the percentage of positive cells in the full thickness of the cartilage), exhibited significant variation in relation to the severity of cartilage degradation. The associations between the subchondral bone properties and zonal and overall expression of these enzymes in the cartilage were generally weak or nonsignificant.

CONCLUSIONS: Phenotypic changes in chondrocytes and remodelling of subchondral bone proceed at different rates throughout the process of cartilage degradation. Biological influences are more important for cartilage degradation at early stages, while biomechanical damage to the compromised tissue may outrun the phenotypic change of chondrocytes and is critical in the advanced stages.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.