Back to Search Start Over

Mesenchymal MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation

Authors :
Fan Zhao
Xiaoli Ma
Wuxia Qiu
Pai Wang
Ru Zhang
Zhihao Chen
Peihong Su
Yan Zhang
Dijie Li
Jianhua Ma
Chaofei Yang
Lei Chen
Chong Yin
Ye Tian
Lifang Hu
Yu Li
Ge Zhang
Xiaoyang Wu
Airong Qian
Source :
Cells, Vol 9, Iss 3, p 616 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

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 will expand the biological scope of the MACF1 gene, and provide an experimental basis for targeting MACF1 in degenerative bone diseases such as osteoporosis.

Details

Language :
English
ISSN :
20734409
Volume :
9
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.f7972a1b9cd94952b1adb45efae7270c
Document Type :
article
Full Text :
https://doi.org/10.3390/cells9030616