title: Expression of CXC chemokines and their receptors is modulated during chondrogenic differentiation of human mesenchymal stem cells grown in three-dimensional scaffold: evidence in native cartilage.
abstract: Chemokines contribute to the maintenance of cartilage homeostasis. To evaluate the role of CXC chemokines CXCL8 (interleukin-8), CXCL10 (interferon-gamma-inducible protein-10), CXCL12 (stroma-derived factor-1) and CXCL13 (B-cell attracting chemokine-1) and their receptors, respectively CXCR1-2, CXCR3, CXCR4, and CXCR5, during chondrogenic differentiation of human mesenchymal stromal cells (h-MSCs), we used a well-defined in vitro model. Chondrogenic differentiation was analyzed on h-MSCs grown on hyaluronic acid-based biomaterial in the presence or absence of transforming growth factor-beta, and the expression and modulation of CXC chemokines and receptors were evaluated at different time points. Real-time polymerase chain reaction was performed to analyze their expression at the messenger ribonucleic acid (mRNA) level, and immunohistochemistry and enzyme-linked immunosorbent assay were used to evaluate their expression at the protein level. Human articular cartilage biopsies were used to evaluate chemokine and receptor expression in normal tissue. We found no expression of CXCR1, CXCR2, CXCR3, or CXCL10 at the mRNA level. CXCL8 mRNA was down-modulated, whereas at the protein level, we found greater release of this chemokine. CXCR4 and its ligand CXCL12 were down-modulated during chondrogenesis. By contrast, CXCR5 was up-regulated, whereas its ligand CXCL13 was lower. These data were also confirmed on human articular cartilage. These findings show that, during in vitro h-MSC chondrogenic differentiation, chemokine and receptor expression was specifically induced or repressed. This was in line with what the authors also found in normal articular cartilage, suggesting a role in differentiation and maturation of a cartilage-like structure in vitro and consequently the regulation of cartilage homeostasis.
authors.affiliation: Laboratory of Immunology and Genetics, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cristino
authors.forename: Anna
authors.initials: A
authors.lastname: Piacentini
authors.forename: Cristina
authors.initials: C
authors.lastname: Manferdini
authors.forename: Katia
authors.initials: K
authors.lastname: Codeluppi
authors.forename: Francesco
authors.initials: F
authors.lastname: Grassi
authors.forename: Andrea
authors.initials: A
authors.lastname: Facchini
authors.forename: Gina
authors.initials: G
authors.lastname: Lisignoli
mesh_terms: D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D054387:Receptors, CXCR / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D019743:Chemokines, CXC; D012333:RNA, Messenger; D054387:Receptors, CXCR; D016212:Transforming Growth Factor beta; D006820:Hyaluronic Acid