잠시만 기다려 주세요. 로딩중입니다.

Macrophage-Stimulating Protein Enhances Osteoblastic Differentiation via the Recepteur d'Origine Nantais Receptor and Extracellular Signal-Regulated Kinase Signaling Pathway

Journal of Bone Metabolism 2020년 27권 4호 p.267 ~ 279
정병철, 오신혜, 이미남, 고정태,
소속 상세정보
정병철 ( Jeong Byung-Chul ) - Chonnam National University School of Dentistry Department of Pharmacology and Dental Therapeutics
오신혜 ( Oh Sin-Hye ) - Chonnam National University School of Dentistry Department of Pharmacology and Dental Therapeutics
이미남 ( Lee Mi-Nam ) - Chonnam National University School of Dentistry Department of Pharmacology and Dental Therapeutics
고정태 ( Koh Jeong-Tae ) - Chonnam National University School of Dentistry Department of Pharmacology and Dental Therapeutics

Abstract


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.

키워드

Cell differentiation; Extracellular signal-regulated MAP kinases; Macrophage stimulating protein; Osteoblasts; Recepteur d'Origine Nantais

원문 및 링크아웃 정보

등재저널 정보