title: Chondrogenic differentiation of human subchondral progenitor cells is impaired by rheumatoid arthritis synovial fluid.
abstract: In microfracture, subchondral progenitors enter the cartilage defect and form cartilage repair tissue. We hypothesize that synovial fluid (SF) from rheumatoid arthritis (RA) donors affects chondrogenesis of human subchondral progenitors stimulated with transforming growth factor-beta3 (TGFB3), whereas SF from normal and osteoarthritis (OA) donors do not. Human progenitors from subchondral cortico-spongious bone (pool of n = 4) were cultured in micromasses under serum-free conditions and were stimulated with 10 ng/mL TGFB3 and with 5% SF from normal, OA, and RA donors (pool of n = 7, each). Histological staining of proteoglycan and immunostaining of type II collagen showed that progenitors stimulated with SF from RA donors show significantly reduced cartilage matrix formation compared to progenitors treated with TGFB3 or with SF from normal and OA donors (n = 3, each). Gene expression analysis of typical chondrocyte marker genes and genes encoding matrix modifying enzymes showed that SF from OA and RA donors influence the onset of TGFB3-mediated chondrogenesis (pool of 20 micromasses), but had no effect on the gene expression profile after prolonged culture in micromasses. These results suggest that SF from RA patients may impair the chondrogenic development of mesenchymal progenitors in microfracture, whereas osteoarthritic SF may has no negative effect on the cartilage matrix formation.
authors.affiliation: TransTissue Technologies GmbH, Berlin, Germany.
authors.forename: Jan Philipp
authors.initials: JP
authors.lastname: Krüger
authors.forename: Michaela
authors.initials: M
authors.lastname: Endres
authors.forename: Katja
authors.initials: K
authors.lastname: Neumann
authors.forename: Thomas
authors.initials: T
authors.lastname: Häupl
authors.forename: Christoph
authors.initials: C
authors.lastname: Erggelet
authors.forename: Christian
authors.initials: C
authors.lastname: Kaps
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D010003:Osteoarthritis / Q000503:physiopathology; D013582:Synovial Fluid / Q000502:physiology*; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology
chemical_list: D053782:Transforming Growth Factor beta3