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Metastasis suppressor 1 controls osteoblast differentiation and bone homeostasis through regulating Src-Wnt/β-catenin signaling

Metastasis suppressor 1 (MTSS1) plays an inhibitory role in tumorigenesis and metastasis of a variety of cancers. To date, the function of MTSS1 in the differentiation of marrow stromal progenitor cells remains to be explored. In the current study, we investigated whether and how MTSS1 has a role in...

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Published in:Cellular and molecular life sciences : CMLS 2022-02, Vol.79 (2), p.107, Article 107
Main Authors: Chen, Meng, Shan, Liying, Gan, Ying, Tian, Lijie, Zhou, Jie, Zhu, Endong, Yuan, Hairui, Li, Xiaoxia, Wang, Baoli
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cited_by cdi_FETCH-LOGICAL-c475t-57e5009c5ec92e3cdbc2c5335a41fb0f6f61b9f39391ea1715e93d6c6b2f5ea93
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container_title Cellular and molecular life sciences : CMLS
container_volume 79
creator Chen, Meng
Shan, Liying
Gan, Ying
Tian, Lijie
Zhou, Jie
Zhu, Endong
Yuan, Hairui
Li, Xiaoxia
Wang, Baoli
description Metastasis suppressor 1 (MTSS1) plays an inhibitory role in tumorigenesis and metastasis of a variety of cancers. To date, the function of MTSS1 in the differentiation of marrow stromal progenitor cells remains to be explored. In the current study, we investigated whether and how MTSS1 has a role in osteoblast differentiation and bone homeostasis. Our data showed that MTSS1 mRNA was upregulated during osteoblast differentiation and downregulated in the osteoblastic lineage cells of ovariectomized and aged mice. Functional studies revealed that MTSS1 promoted the osteogenic differentiation from marrow stromal progenitor cells. Mechanistic explorations uncovered that the inactivation of Src and afterward activation of canonical Wnt signaling were involved in osteoblast differentiation induced by MTSS1. The enhanced osteogenic differentiation induced by MTSS1 overexpression was attenuated when Src was simultaneously overexpressed, and conversely, the inhibition of osteogenic differentiation by MTSS1 siRNA was rescued when the Src inhibitor was supplemented to the culture. Finally, the in vivo transfection of MTSS1 siRNA to the marrow of mice significantly reduced the trabecular bone mass, along with the reduction of trabecular osteoblasts, the accumulation of marrow adipocytes, and the increase of phospho-Src-positive cells on the trabeculae. No change in the number of osteoclasts was observed. This study has unraveled that MTSS1 contributes to osteoblast differentiation and bone homeostasis through regulating Src-Wnt/β-catenin signaling. It also suggests the potential of MTSS1 as a new target for the treatment of osteoporosis.
doi_str_mv 10.1007/s00018-022-04147-y
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1420-9071
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subjects Adipocytes
Animals
beta Catenin - genetics
beta Catenin - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedical materials
Biomedicine
Blotting, Western
Bone and Bones - metabolism
Bone marrow
Bone mass
Bone turnover
Cancellous bone
Cell Biology
Cell culture
Cell differentiation
Cell Differentiation - genetics
Cells (biology)
Cells, Cultured
Differentiation (biology)
Female
Gene Expression Regulation
Homeostasis
Homeostasis - genetics
Humans
Inactivation
Life Sciences
Metastases
Metastasis
Mice
Mice, Inbred C57BL
Microfilament Proteins - genetics
Microfilament Proteins - metabolism
mRNA
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Original
Original Article
Osteoblastogenesis
Osteoblasts
Osteoblasts - cytology
Osteoblasts - metabolism
Osteoclasts
Osteogenesis - genetics
Osteoporosis
Ovariectomy
Progenitor cells
Reverse Transcriptase Polymerase Chain Reaction
Signaling
siRNA
src-Family Kinases - genetics
src-Family Kinases - metabolism
Stem cells
Transfection
Tumorigenesis
Wnt protein
Wnt Signaling Pathway - genetics
β-Catenin
title Metastasis suppressor 1 controls osteoblast differentiation and bone homeostasis through regulating Src-Wnt/β-catenin signaling
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