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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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Background: Macrophage-stimulating protein (MSP; also known as macrophage stimulating 1 and hepatocyte growth factor-like protein) has been shown to play a crucial role in calcium homeostasis and skeletal mineralization in zebrafish. However, the precise role of MSP in osteoblasts has not been elucidated. In this study, we investigated the effect of MSP on osteoblast differentiation of pre-osteoblast cells. Methods: Osteoblast differentiation upon MSP treatment was evaluated by analyzing the osteogenic gene expression, alkaline phosphatase (ALP) activity, and mineralized nodule formation. To assess changes in the MSP-RON signaling pathway, knockdown of Ron gene was performed using siRNA and pharmacological inhibitor treatment. Results: Expression of the tyrosine kinase receptor RON, a receptor of MSP, was found to be significantly increased during osteoblast differentiation. MSP treatment significantly upregulated the expression of osteogenic marker genes and remarkably increased ALP activity and mineralized nodule formation. Conversely, knockdown of Ron significantly attenuated the expression of osteogenic marker genes and ALP activity that were induced upon MSP treatment. Mechanistically, MSP treatment significantly enhanced the phosphorylation of extracellular signal-regulated kinase (ERK); however, additional treatment with the selective ERK inhibitor PD98059 attenuated the effect of MSP on osteoblast differentiation. Conclusions: Altogether, these results indicate that the MSP-RON axis is involved in promoting osteoblast differentiation via activation of the ERK signaling pathway.
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참고문헌 (42)
참고문헌 신청
Natalie A Sims / 2014 / Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit / BoneKEy Reports 3
Lifang Hu / 2018 / Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment / International Journal of Molecular Sciences 19(2):360
Xu Feng / 2011 / Disorders of Bone Remodeling / Annual Review of Pathology: Mechanisms of Disease 6(1):121~145
Shun-ichi Harada / 2003 / Control of osteoblast function and regulation of bone mass / Nature 423(6937):349~355
M. Wang / 1994 / Identification of the ron gene product as the receptor for the human macrophage stimulating protein / Science 266(5182):117~119
Lifang Hu / 2018 / Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment / International Journal of Molecular Sciences 19(2):360
Xu Feng / 2011 / Disorders of Bone Remodeling / Annual Review of Pathology: Mechanisms of Disease 6(1):121~145
Shun-ichi Harada / 2003 / Control of osteoblast function and regulation of bone mass / Nature 423(6937):349~355
M. Wang / 1994 / Identification of the ron gene product as the receptor for the human macrophage stimulating protein / Science 266(5182):117~119
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