Protein Expression Analysis in Hematopoietic Stem Cells during Osteopontin-Induced Differentiation of Natural Killer Cells

Abstract

Natural Killer (NK) cells are the lymphocytes that are derived from hematopoietic stem cells, developed in the bone marrow from hematopoietic stem cells (HSC) by sequential acquisition of functional surface receptors, and express the repertoire of inhibitory and activating receptors. Recently, Osteopontin (OPN) has been identifi ed as a critical factor for differentiation of natural killer cells. However, the detailed mechanism of OPN-induced NK differentiation has been still to be elucidated. Here, we determined the signaling pathway and possible receptor for OPN in NK differentiation. OPN induced expression of Bcl-2 and activation of Erk kinase. Inhibition of Erk pathway decreased the effect of OPN on NK differentiation. In addition, the expression of integrin α9 was signifi cantly increased by OPN during NK differentiation, suggesting the possible role of a major signaling molecule for OPN-induced NK differentiation. (Chung et al., 2008). OPN is a secreted protein which is mainly expressed in bone marrow stromal cells. OPN has been known to play a variety of roles in cellular mechanisms including proliferation, apoptosis, and migration. In addition, OPN has been reported to act as a negative regulator of HSC although the effect of OPN on HSC proliferation or apoptosis is controversial. For example, it was shown that OPN reduces the number of HSCs by inhibition of proliferation while increasing apoptosis (Stier et al., 2005). On the contrary, it has been reported that OPN negatively regulates HSC proliferation in-