title: Interleukin 17 inhibits progenitor cells in rheumatoid arthritis cartilage.
abstract: Mesenchymal stem cells are known to exert immunomodulatory effects in inflammatory diseases. Immuneregulatory cells lead to progressive joint destruction in rheumatoid arthritis (RA). Proinflammatory cytokines, such as tumour necrosis factor α (TNF-α) and interleukins (ILs) are the main players. Here, we studied progenitor cells from RA cartilage (RA-CPCs) that are positive for IL-17 receptors to determinate the effects of inflammation on their chondrogenic potenial. IL-17A/F reduced the chondrogenic potential of these cells via the upregulation of RUNX2 protein and enhanced IL-6 protein and MMP3 mRNA levels. Blocking antibodies against IL-17 positively influenced their repair potential. Furthermore, treating the RA-CPCs with the anti-human IL-17 antibody secukinumab or the anti-TNF-α antibody adalimumab reduced the proinflammatory IL-6 protein level and positively influenced the secretion of anti-inflammatory IL-10 protein. Additionally, adalimumab and secukinumab in particular reduced RUNX2 protein to promote chondrogenesis. The amelioration of inflammation, particularly via IL-17 antagonism, might be a new therapeutic approach for enhancing intrinsic cartilage repair mechanisms in RA patients.
authors.affiliation: Department of Prosthodontics, Tissue Regeneration Work Group, University Medical Center, Goettingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Schminke
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center, Goettingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Trautmann
authors.affiliation: VitosOrthopaedic Clinic, Kassel, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Mai
authors.affiliation: Department of Prosthodontics, Tissue Regeneration Work Group, University Medical Center, Goettingen, Germany.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Miosge
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center, Goettingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Blaschke
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage; D000368:Aged; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy; D002356:Cartilage / Q000473:pathology; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects / Q000276:immunology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050659:Core Binding Factor Alpha 1 Subunit; D016207:Cytokines; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; C555450:secukinumab; D019278:Matrix Metalloproteinase 3; D000068879:Adalimumab
keywords: Cartilage Chondrogenesis ⋅ Chondrogenic progenitor cells ⋅ Rheumatoid arthritis ⋅ Interleukin 17 (IL-17)