title: Are chondrocytes damaged when rheumatologic inflammation is suppressed?
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Physical Medicine and Rehabilitation , School of Medicine, Namik Kemal University , Tekirdag , Turkey.
authors.forename: Aliye Yildirim
authors.initials: AY
authors.lastname: Guzelant
authors.affiliation: b Department of Orthopaedic and Traumatology , School of Medicine, Istanbul Medipol University , Istanbul , Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Isyar
authors.affiliation: c Department of Pharmacovigilance and Rational Drug Use Team , Republic of Turkey Ministry of Health, State Hospital , Tekirdag , Turkey.
authors.forename: İbrahim
authors.initials: İ
authors.lastname: Yilmaz
authors.affiliation: d Deparment of Molecular Biology and Genetics , Faculty of Science, Namik Kemal University , Tekirdag , Turkey , and.
authors.forename: Duygu Yasar
authors.initials: DY
authors.lastname: Sirin
authors.affiliation: e Department of Orthopaedic and Traumatology , Gulhane Military Medical Academy, Haydarpasa Training Hospital , Istanbul , Turkey.
authors.forename: Selami
authors.initials: S
authors.lastname: Cakmak
authors.affiliation: b Department of Orthopaedic and Traumatology , School of Medicine, Istanbul Medipol University , Istanbul , Turkey.
authors.forename: Mahir
authors.initials: M
authors.lastname: Mahirogullari
mesh_terms: D000069594:Abatacept / Q000009:adverse effects*; D000068879:Adalimumab / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D005269:Femur / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008855:Microscopy, Electron, Scanning; D055034:Osteochondrosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000069283:Rituximab / Q000009:adverse effects*; D013977:Tibia / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab; D000069594:Abatacept; D000068879:Adalimumab
keywords: Abatacept; adalimumab; cell culture; chondrotoxicity; rituximab