title: Hyaluronan-based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of Cd44 and Cd54.
abstract: Hyaluronan (HA), in the bone marrow stroma, is the major non-protein glycosaminoglycan component of extracellular matrix (ECM) involved in cell positioning, proliferation, differentiation as well as in receptor-mediated changes in gene expression. Repair of bone and regeneration of bone marrow is dependent on ECM, inflammatory factors, like chemokines and degradative factors, like metalloproteinases. We analyzed the interaction between human mesenchymal stem cells (h-MSCs) and a three-dimensional (3-D) HA-based scaffold in vitro. The expression of CXC chemokines/receptors, CXCL8 (IL-8)/CXCR1-2, CXCL10 (IP-10)/CXCR3, CXCL12 (SDF-1)/CXCR4, and CXCL13 (BCA-1)/CXCR5, and metalloproteinases/inhibitors MMP-1, MMP-3, MMP-13/TIMP-1 were evaluated in h-MSCs grown on plastic or on HA-based scaffold by Real-time PCR, ELISA, and immunocytochemical techniques. Moreover, the expression of two HA receptors, CD44 and CD54, was analyzed. We found both at mRNA and protein levels that HA-based scaffold induced the expression of CXCR4, CXCL13, and MMP-3 and downmodulated the expression of CXCL12, CXCR5, MMP-13, and TIMP-1 while HA-based scaffold induced CD54 expression but not CD44. We found that these two HA receptors were directly involved in the modulation of CXCL12, CXCL13, and CXCR5. This study demonstrates a direct action of a 3-D HA-based scaffold, widely used for cartilage and bone repair, in modulating both h-MSCs inflammatory and degradative factors directly involved in the engraftment of specific cell types in a damaged area. Our data clearly demonstrate that HA in this 3-D conformation acts as a signaling molecule for h-MSCs.
authors.affiliation: Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy. labimge@alma.unibo.it
authors.forename: Gina
authors.initials: G
authors.lastname: Lisignoli
authors.forename: Sandra
authors.initials: S
authors.lastname: Cristino
authors.forename: Anna
authors.initials: A
authors.lastname: Piacentini
authors.forename: Carola
authors.initials: C
authors.lastname: Cavallo
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Caplan
authors.forename: Andrea
authors.initials: A
authors.lastname: Facchini
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; C497483:CD44 protein, human; C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D018960:Hyaluronan Receptors; D018836:Inflammation Mediators; D007375:Interleukin-1; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D006820:Hyaluronic Acid; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3