JNK regulates osteoblast differentiation through Id4

What is it about?

Osteoblasts are multi-functional cells controlling bone metabolism and immune responses by producing bone matrix proteins. Osteopontin (OPN) and osteocalcin (OCN) are secreted from osteoblasts at various expression levels depending on the maturation level of osteoblasts. OPN stimulates bone resorption by inducing adhesion, migration and differentiation of osteoclasts. OCN is widely used as a clinical examination marker of bone formation and has important roles in the regulation of glucose metabolism Thus, Secretory amounts and patterns of OPN and OCN directly characterize diverse roles of osteoblasts in whole body metabolism. OPN is known to be specifically expressed in middle stage of osteogenesis. Conversely, OCN is expressed in the late stage and regarded as a maturation marker of osteoblastic differentiation. However, previous studies indicated that differentiated osteoblasts comprise phenotypically distinct groups, suggesting that osteoblastic differentiation is multi-directional rather than uni-directional. Thus, we hypothesized that there are distinct groups of differentiated osteoblasts with different expression patterns of bone matrix proteins including OPN and OCN. In this study, we showed that the inhibition of JNK, a member of the mitogen-activated protein kinase family, regulates osteoblast differentiation balance toward OPN high expression type rather than the regularly differentiated phenotype. OPN-type osteoblasts expressed specific cytokines, transcriptional factors and cell surface markers. Moreover, we found that the molecular complex of inhibitor of differentiation/DNA binding (Id4) and DUSP16 is critically involved in OPN-type osteoblast induction. In conclusion, our data indicated that osteoblast differentiation might be multi-directional to regulate bone-derived cytokine expression.

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