Mesenchymal MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation.

Cells
Fan ZhaoAirong Qian

Abstract

Microtubule actin crosslinking factor 1 (MACF1) is a large crosslinker that contributes to cell integrity and cell differentiation. Recent studies show that MACF1 is involved in multiple cellular functions such as neuron development and epidermal migration, and is the molecular basis for many degenerative diseases. MACF1 is highly abundant in bones, especially in mesenchymal stem cells; however, its regulatory role is still less understood in bone formation and degenerative bone diseases. In this study, we found MACF1 expression in mesenchymal stem cells (MSCs) of osteoporotic bone specimens was significantly lower. By conditional gene targeting to delete the mesenchymal Macf1 gene in mice, we observed in MSCs decreased osteogenic differentiation capability. During early stage bone development, the MACF1 conditional knockout (cKO) mice exhibit significant ossification retardation in skull and hindlimb, and by adulthood, mesenchymal loss of MACF1 attenuated bone mass, bone microarchitecture, and bone formation capability significantly. Further, we showed that MACF1 interacts directly with SMAD family member 7 (SMAD7) and facilitates SMAD7 nuclear translocation to initiate downstream osteogenic pathways. Hopefully these findings ...Continue Reading

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Citations

Oct 22, 2020·Critical Reviews in Biochemistry and Molecular Biology·Charlotte de Ceuninck van CapellePeter Ten Dijke
Jun 17, 2021·Journal of Cellular and Molecular Medicine·Chong YinAirong Qian

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Datasets Mentioned

BETA
GSE12274

Methods Mentioned

BETA
transfection
Knockout
PCR
chips
confocal microscopy
electrophoresis
X-ray
enzyme-linked immunosorbent assay
ELISA
immunoprecipitation

Software Mentioned

Image
ImageJ
Adobe Photoshop
Pro Plus
MicroView
Histomorph suite

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