Role of Cytokines Signaling in Osteoblastic Differentiation

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1) Role of IL-6 in osteoblastic differentiationWe determined whether IL-6 plays a role in osteoblastogenesis using pluripotent mesenchymal cell line C3H10T1/2. IL-6 induced osteoblastic differentiation of C3H10T1/2 in the presence of sIL-6R, but not in the absence of it. One of IL-6 family cytokine, Oncostatin M also showed quite similar effects on C3H10T1/2. The data suggest that IL-6/sIL-6R is involved in osteoblastic differentiation of pluripotent mesenchymal cells.2) Activation of IL-6 signaling during osteoblactic differentiationTo understand the molecular mechanisms by which IL-6 differentiates C3H10T1/2 into osteoblastic cells, we first determined the intracellular signaling cascade of IL-6 in C3H10T1/2. IL-6/sIL-6R induced tyrosine phosphorylation of gp130, JAK1, and JAK2. STAT1 and STAT3 were tyrosine-phosphorylated by IL-6/sIL-6R treatment, and translocated from cytoplasm into nucleus. IL-6/sIL-6R also activated MAP kinase. These results indicate that IL-6/sIL-6R concomitantl … More y activate JAK/STAT and MAP kinase pathway in C3H10T1/2.3) Role of JAK/STAT and MAP kinase signaling in osteoblastic differentiationIn order to investigate the functional role of JAK/STAT signaling in osteoblastic differentiation, we examined the effects of dominant negative JAK1 (DN-JAK1) or JAK2 (DN-JAK2) on IL-6 induced osteoblastic differentiation. DN-JAK1 as well as DN-JAK2 blocked activation of JAK/STAT signaling. DN-JAK1 and DN-JAK2 also blocked IL-6 induced osteoblastic differentiation of C3H10T1/2. We, next, studied the role of MAP kinases in osteoblastic differentiation using dominant negative ras (DN-ras). DN-ras inhibited activation of MAP kinases. DN-ras partially inhibited activation of STAT and osteoblastic differentiation of C3H10T1/2. The data indicated that essential role of JAK/STAT signaling and the involvement of cross talk between JAK/STAT and MAP kinase signaling in osteoblastic differentiation induced by IL-6.4) BMP2 signaling that regulates osteoblastic differentiationWe found BMP2 induced osteoblastic differentiation by inducing expression of Cbfa1 via activation of Smad signaling. Less