PMID- 31903103
OWN - NLM
STAT- MEDLINE
DCOM- 20210402
LR  - 20210402
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 10
IP  - 1
DP  - 2020
TI  - Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization 
      by activating PI3K/AKT/GSK3beta/beta-catenin pathway.
PG  - 17-35
LID - 10.7150/thno.36930 [doi]
AB  - Approximately 10% of bone fractures do not heal satisfactorily, leading to 
      significant clinical and socioeconomic implications. Recently, the role of 
      macrophages in regulating bone marrow stem cell (BMSC) differentiation through 
      the osteogenic pathway during fracture healing has attracted much attention. 
      Methods: The tibial monocortical defect model was employed to determine the 
      critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous 
      ossification (IO) in vivo. The potential functions and mechanisms of MSR1 were 
      explored in a co-culture system of bone marrow-derived macrophages (BMDMs), 
      RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and 
      RNA sequencing. Results: In this study, using the tibial monocortical defect 
      model, we observed delayed IO in MSR1 knockout (KO) mice compared to MSR1 
      wild-type (WT) mice. Furthermore, macrophage MSR1 mediated 
      PI3K/AKT/GSK3beta/beta-catenin signaling increased ability to promote osteogenic 
      differentiation of BMSCs in the co-culture system. We also identified 
      proliferator-activated receptor gamma coactivator 1-alpha (PGC1alpha) as the target 
      gene for macrophage MSR1-activated PI3K/AKT/GSK3beta/beta-catenin pathway in the 
      co-culture system that facilitated M2-like polarization by enhancing 
      mitochondrial oxidative phosphorylation. Conclusion: Our findings revealed a 
      previously unrecognized function of MSR1 in macrophages during fracture repair. 
      Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture 
      repair.
CI  - (c) The author(s).
FAU - Zhao, Shu-Jie
AU  - Zhao SJ
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Kong, Fan-Qi
AU  - Kong FQ
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Jie, Jian
AU  - Jie J
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
AD  - Department of Orthopedics, Pukou Branch of JiangSu Province Hospital (Nanjing 
      Pukou Central Hospital), Nanjing, 211800, China.
FAU - Li, Qing
AU  - Li Q
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 
      200240, China.
FAU - Liu, Hao
AU  - Liu H
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Xu, An-Di
AU  - Xu AD
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative 
      Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing 
      Medical University, Nanjing, 211100, China.
FAU - Yang, Ya-Qing
AU  - Yang YQ
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative 
      Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing 
      Medical University, Nanjing, 211100, China.
FAU - Jiang, Bin
AU  - Jiang B
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative 
      Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing 
      Medical University, Nanjing, 211100, China.
FAU - Wang, Dong-Dong
AU  - Wang DD
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative 
      Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing 
      Medical University, Nanjing, 211100, China.
FAU - Zhou, Zhong-Qiu
AU  - Zhou ZQ
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative 
      Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing 
      Medical University, Nanjing, 211100, China.
FAU - Tang, Peng-Yu
AU  - Tang PY
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Chen, Jian
AU  - Chen J
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Zhou, Zheng
AU  - Zhou Z
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Chen, Qi
AU  - Chen Q
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative 
      Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing 
      Medical University, Nanjing, 211100, China.
FAU - Yin, Guo-Yong
AU  - Yin GY
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
FAU - Zhang, Han-Wen
AU  - Zhang HW
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative 
      Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing 
      Medical University, Nanjing, 211100, China.
FAU - Fan, Jin
AU  - Fan J
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, 210029, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200101
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Msr1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class A)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Macrophages/cytology/*metabolism
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Osteogenesis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RAW 264.7 Cells
MH  - Scavenger Receptors, Class A/*metabolism
MH  - *Signal Transduction
MH  - beta Catenin/metabolism
PMC - PMC6929615
OTO - NOTNLM
OT  - Bone marrow stem cells
OT  - Macrophage scavenger receptor 1
OT  - Osteogenic differentiation
OT  - Oxidative phosphorylation
OT  - PI3K/AKT/GSK3beta/beta-catenin pathway
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/01/07 06:00
MHDA- 2021/04/07 06:00
PMCR- 2020/01/01
CRDT- 2020/01/07 06:00
PHST- 2019/05/23 00:00 [received]
PHST- 2019/09/21 00:00 [accepted]
PHST- 2020/01/07 06:00 [entrez]
PHST- 2020/01/07 06:00 [pubmed]
PHST- 2021/04/07 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - thnov10p0017 [pii]
AID - 10.7150/thno.36930 [doi]
PST - epublish
SO  - Theranostics. 2020 Jan 1;10(1):17-35. doi: 10.7150/thno.36930. eCollection 2020.