Evaluation of the Anti-Inflammatory and Chondroprotective Effect of Celecoxib on Cartilage Ex Vivo and in a Rat Osteoarthritis Model.

Autor: Haartmans MJJ; Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University, Maastricht, The Netherlands.; Maastricht MultiModal Molecular Imaging Institute (M4i), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands., Timur UT; Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University, Maastricht, The Netherlands., Emanuel KS; Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University, Maastricht, The Netherlands.; Department of Orthopaedic Surgery, Amsterdam Movement Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Caron MMJ; Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University, Maastricht, The Netherlands., Jeuken RM; Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University, Maastricht, The Netherlands., Welting TJM; Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University, Maastricht, The Netherlands., van Osch GJVM; Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Heeren RMA; Maastricht MultiModal Molecular Imaging Institute (M4i), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands., Cillero-Pastor B; Maastricht MultiModal Molecular Imaging Institute (M4i), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands.; MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht University, Maastricht, The Netherlands., Emans PJ; Laboratory for Experimental Orthopedics, Joint Preserving Clinic, Department of Orthopaedic Surgery, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: Cartilage [Cartilage] 2022 Jul-Sep; Vol. 13 (3), pp. 19476035221115541.
DOI: 10.1177/19476035221115541
Abstrakt: Objective: The potential chondroprotective effect of celecoxib, a nonsteroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor used to reduce pain and inflammation in knee osteoarthritis patients, is disputed. This study aimed at investigating the chondroprotective effects of celecoxib on (1) human articular cartilage explants and (2) in an in vivo osteoarthritis rat model.
Design: Articular cartilage explants from 16 osteoarthritis patients were cultured for 24 hours with celecoxib or vehicle. Secreted prostaglandins (prostaglandin E 2 , prostaglandin F 2α , prostaglandin D 2 ) and thromboxane B2 (TXB2) concentrations were determined in medium by ELISA, and protein regulation was measured with label-free proteomics. Cartilage samples from 7 of these patients were analyzed for gene expression using real-time quantitative polymerase chain reaction. To investigate the chondroprotective effect of celecoxib in vivo , 14 rats received an intra-articular injection of celecoxib or 0.9% NaCl after osteoarthritis induction by anterior cruciate ligament transection and partial medial meniscectomy (ACLT/pMMx model). Histopathological scoring was used to evaluate osteoarthritis severity 12 weeks after injection.
Results: Secretion of prostaglandins, target of Nesh-SH3 (ABI3BP), and osteonectin proteins decreased, whereas tissue inhibitor of metalloproteinase 2 (TIMP-2) increased significantly after celecoxib treatment in the human ( ex vivo ) explant culture. Gene expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS4/5) and metalloproteinase 13 (MMP13) was significantly reduced after celecoxib treatment in human cartilage explants. Cartilage degeneration was reduced significantly in an in vivo osteoarthritis knee rat model.
Conclusions: Our data demonstrated that celecoxib acts chondroprotective on cartilage ex vivo and a single intra-articular bolus injection has a chondroprotective effect in vivo .
Databáze: MEDLINE
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