PMID- 34621738
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211009
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 9
DP  - 2021
TI  - Macrophage-Mediated Bone Formation in Scaffolds Modified With MSC-Derived 
      Extracellular Matrix Is Dependent on the Migration Inhibitory Factor Signaling 
      Pathway.
PG  - 714011
LID - 10.3389/fcell.2021.714011 [doi]
LID - 714011
AB  - The positive role of macrophages in the osteogenesis of mesenchymal stem cells 
      (MSCs) has been a recent research focus. On the other hand, MSCs could carefully 
      regulate the paracrine molecules derived from macrophages. Human umbilical cord 
      mesenchymal stem cells (hucMSCs) can reduce the secretion of inflammatory factors 
      from macrophages to improve injury healing. hucMSC-derived extracellular matrix 
      (hucMSC-ECM) has the similar effect to hucMSCs, which could combat the 
      inflammatory response of macrophages. Additionally, MSC-derived extracellular 
      matrix also enhanced bone regeneration by inhibiting osteoclastic differentiation 
      of monocyte/macrophage lineage. However, whether hucMSC-ECM could improve bone 
      formation by guiding macrophage-induced osteogenic differentiation of MSCs is 
      unknown. Here, we present decalcified bone scaffolds modified by hucMSC-derived 
      extracellular matrix (DBM-ECM), which maintained multiple soluble cytokines from 
      hucMSCs, including macrophage migration inhibitory factor (MIF). Compared with 
      DBM, the DBM-ECM scaffolds induced bone formation in an improved heterotopic 
      ossification model of severe combined immunodeficiency (SCID) mice in a 
      macrophage-dependent manner. Macrophages cocultured with DBM-ECM expressed four 
      osteoinductive cytokines (BMP2, FGF2, TGFbeta3 and OSM), which were screened out by 
      RNA sequencing and measured by qPCR and western blot. The conditioned medium from 
      macrophages cocultured with DBM-ECM improved the osteogenic differentiation of 
      hBMSCs. Furthermore, DBM-ECM activated CD74/CD44 (the typical MIF receptors) 
      signal transduction in macrophages, including phosphorylation of P38 and 
      dephosphorylation of c-jun. On the other side, the inhibitory effects of the 
      DBM-ECM scaffolds with a deficient of MIF on osteogenesis in vitro and in vivo 
      revealed that macrophage-mediated osteogenesis depended on MIF/CD74 signal 
      transduction. The results of this study indicate that the coordinated crosstalk 
      of macrophages and MSCs plays a key role on bone regeneration, with an emphasis 
      on hucMSC-ECM constructing a macrophage-derived osteoinductive microenvironment.
CI  - Copyright (c) 2021 Deng, Tan, Dai, Luo and Xu.
FAU - Deng, Moyuan
AU  - Deng M
AD  - Department of Orthopaedics, Southwest Hospital, Army Medical University, 
      Chongqing, China.
FAU - Tan, Jiulin
AU  - Tan J
AD  - Department of Orthopaedics, Southwest Hospital, Army Medical University, 
      Chongqing, China.
FAU - Dai, Qijie
AU  - Dai Q
AD  - Department of Orthopaedics, Southwest Hospital, Army Medical University, 
      Chongqing, China.
FAU - Luo, Fei
AU  - Luo F
AD  - Department of Orthopaedics, Southwest Hospital, Army Medical University, 
      Chongqing, China.
FAU - Xu, Jianzhong
AU  - Xu J
AD  - Department of Orthopaedics, Southwest Hospital, Army Medical University, 
      Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20210921
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8490662
OTO - NOTNLM
OT  - extracellular matrix
OT  - macrophages
OT  - mesenchymal stem cells
OT  - migration inhibitory factor
OT  - osteogenic differentiation
OT  - osteoimmunological microenviroment
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/10/09 06:00
MHDA- 2021/10/09 06:01
PMCR- 2021/01/01
CRDT- 2021/10/08 07:12
PHST- 2021/05/24 00:00 [received]
PHST- 2021/08/09 00:00 [accepted]
PHST- 2021/10/08 07:12 [entrez]
PHST- 2021/10/09 06:00 [pubmed]
PHST- 2021/10/09 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2021.714011 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Sep 21;9:714011. doi: 10.3389/fcell.2021.714011. 
      eCollection 2021.