Macrophage-stimulating protein (MSP) is a serum protein that is activated by members of the coagulation cascade in response to tissue damage. A recent study showed that MSP plays an important role in calcium homeostasis and skeletal mineralisation in zebrafish. However, the precise role of MSP in osteoblast differentiation is not fully understood. In this study, we examined the effect of MSP on osteoblastic differentiation from the mesenchymal lineage C3H10T1/2 cells. Expression of receptor tyrosine kinase RON, which is identified as a receptor for MSP, was significantly increased during osteoblast differentiation, and stimulation by MSP increased the expression of osteogenic markers including alkaline phosphatase (ALP), osteocalcin, and osterix. Furthermore, MSP treatment remarkably enhanced ALP enzyme activity and mineralised nodule formation. Conversely, knockdown of receptor RON attenuated the expression of osteogenic markers by MSP treatment. In MSP-treated cells, the phosphorylation of mitogen-activated protein kinase ERK was significantly increased, and additional treatment with the selective ERK inhibitor PD98059 attenuated the effect of MSP on osteoblast differentiation. Taken together, these results suggest that MSP/RON axis can promote osteoblast differentiation via activation of the ERK signalling pathway.
Disclosure: The authors declared no competing interests. This work was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIP)(No. 2011-0030121).