Gp130 activation by soluble interleukin-6 receptor/interleukin-6 enhances osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells.
Interleukin-6 (IL-6) promotes osteodifferentiation in bone-located progenitors; however, it is not known whether this cytokine affects the differentiation of bone marrow-located osteoprogenitors. To address this issue, we prepared human bone marrow-derived mesenchymal stem cells (MSCs), which were characterized by a cell surface phenotype and multipotential nature. It was observed that in the presence of IL-6, MSCs were not differentiated into the osteogenic lineage, as evidenced by a failure to induce alkaline phosphatase activity, an earlier marker of osteodifferentiation. The lack of effect of IL-6 correlates with the observation that MSCs do not express a membrane-bound or soluble IL-6 receptor (sIL-6R). The incompetence of IL-6 was not reversed by the addition of sIL-6R alone or the sIL-6R/IL-6 complex, as it occurs in other IL-6R-negative cells. However, after MSC osteocommittment by dexamethasone, sIL-6R or the sIL-6R/IL-6 complex enhanced alkaline phosphatase activity. The effect of sIL-6R or sIL-6R/IL-6 proved to be dependent on gp130 availability, which is expressed by MSCs, and involves stat-3 phosphorylation. These data suggest that IL-6R deficiency may represent for bone marrow-located mesenchymal progenitors a sort of protective mechanism to escape the osteogenic effect of IL-6, which is produced by the MSC itself as well as by other marrow stromal cells.
Erices
Alejandro
A
Programa Terapias Génicas y Celulares, INTA, Universidad de Chile, Santiago, Chile. aerices@uec.inta.uchile.cl
Conget
Paulette
P
Rojas
Cecilia
C
Minguell
José J
JJ
D000469:Alkaline Phosphatase / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D003907:Dexamethasone / Q000494:pharmacology; D005819:Genetic Markers / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D005819:Genetic Markers; D005938:Glucocorticoids; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D003907:Dexamethasone; D000469:Alkaline Phosphatase