Are chondrocytes damaged when rheumatologic inflammation is suppressed?

Guzelant A. Y., Isyar M., Yilmaz İ., Sirin D. Y., Cakmak S., Mahirogullari M.

Drug and Chemical Toxicology, vol.40, no.1, pp.13-23, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 40 Issue: 1
  • Publication Date: 2017
  • Doi Number: 10.3109/01480545.2016.1166249
  • Journal Name: Drug and Chemical Toxicology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.13-23
  • Keywords: Abatacept, adalimumab, cell culture, chondrotoxicity, rituximab
  • Istanbul Medipol University Affiliated: Yes


Aim: The use of biological agents (BAs) for treating diseases such as rheumatoid arthritis (RA), spondyloarthropathy, and systemic lupus erythematosus to reduce inflammation has been fruitful. Especially as part of the increasing number of studies on the intra-articular application of BAs, the effects of BAs on cartilage have been widely investigated. In the present study, the effects of rituximab, abatacept, and adalimumab, all approved antirheumatic agents, on human primary chondrocytes were investigated comparatively and on the molecular level through viability, proliferation, and toxicity analyses. Materials and methods: Osteochondral tissues from the distal femur and proximal tibia were resected during total knee arthroplasty from patients (n = 3) with confirmed gonarthrosis in whom all medical or conservative treatments had failed. Standard human primary chondrocyte cell culturing was carried out. Immunophenotyping was performed on the cells that adhered to the flask, and their chondrotoxicity was observed using a flow cytometry device. Images of the cells showing chondrotoxicity were analyzed using invert and environmental scanning microscopes, and microimages were obtained. The MTT-enzyme linked immunosorbent assay was performed to observe the toxic effects of BAs on the proliferation of chondrocytes at 24 and 48 h. The results were analyzed using the number of cells and proliferation; statistical comparisons among the groups were carried out using one-way ANOVA. The alpha significance level was set at <0.01. Results: These pharmaceutical agents were chondrotoxic, especially on viability and proliferation (p = 0.0000). Conclusion: BAs are generally used during active inflammation, and following the management of inflammation, their dosage should be determined taking into consideration their cellular-level toxic effects on chondrocytes.