Interleukin‐1β and tumor necrosis factor α inhibit chondrogenesis by human mesenchymal stem cells through NF‐κB–dependent pathways

• DOI: 10.1002/art.24352
• Publication Date: 2009-02-26T13:15:27Z
• Authors: N. Wehling; G. D. Palmer; C. Pilapil; F. Liu; J. W. Wells; P. E. Müller; C. H. Evans; R. M. Porter
• Keywords: Chondrogenesis

Abstract Objective The differentiation of mesenchymal stem cells (MSCs) into chondrocytes provides an attractive basis for the repair and regeneration articular cartilage. Under clinical conditions, chondrogenesis will often need to occur in presence mediators inflammation produced response injury or disease. purpose this study was examine effects 2 important inflammatory cytokines, interleukin‐1β (IL‐1β) tumor necrosis factor α (TNFα), on chondrogenic behavior human MSCs. Methods Aggregate cultures MSCs recovered from femoral intermedullary canal were used. Chondrogenesis assessed by expression relevant transcripts quantitative reverse transcription–polymerase chain reaction analysis examination aggregates histologic immunohistochemical analyses. possible involvement NF‐κB mediating IL‐1β examined delivering a luciferase reporter construct dominant‐negative inhibitor (suppressor‐repressor form IκB [srIκB]) with adenovirus vectors. Results Both TNFα inhibited dose‐dependent manner. This associated marked activation NF‐κB. Delivery srIκB abrogated rescued response. Although type X collagen followed pattern, other markers hypertrophic responded differently. Matrix metalloproteinase 13 induced NF‐κB–dependent Alkaline phosphatase activity, contrast, regardless delivery. Conclusion Cell‐based lesions cartilage be compromised inflamed joints. Strategies enabling under these conditions include use specific antagonists individual pyrogens, such as TNFα, targeting intracellular mediators,