PMID- 34101158
OWN - NLM
STAT- MEDLINE
DCOM- 20220110
LR  - 20220110
IS  - 1473-2262 (Electronic)
IS  - 1473-2262 (Linking)
VI  - 41
DP  - 2021 Jun 8
TI  - Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes.
PG  - 648-667
LID - 10.22203/eCM.v041a42 [doi]
AB  - Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently 
      found in patients suffering from chronic low-back pain. Marrow fibrosis is a 
      hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other 
      fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present 
      study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of 
      BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion 
      from MC1 and adjacent control vertebrae. Frequency of colony-forming unit 
      fibroblast (CFU-F), expression of stem cell surface markers, differentiation 
      capacity, transcriptome, matrix adhesion, cell contractility as well as 
      expression of pro-collagen type I alpha 1, alpha-smooth muscle actin, integrins and 
      focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of 
      C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating 
      overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis 
      showed enrichment in extracellular matrix proteins and fibrosis-related 
      signalling genes. Increases in pro-collagen type I alpha 1 expression, cell 
      adhesion, cell contractility and phosphorylation of FAK provided further evidence 
      for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing 
      (LEPRhigh) BMSC population was identified that differentiated under transforming 
      growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control 
      BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC 
      subpopulation susceptible to myofibroblast differentiation were found. Fibrosis 
      is a hallmark of MC1 and a potential therapeutic target. A causal link between 
      the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.
FAU - Heggli, I
AU  - Heggli I
AD  - Centre of Experimental Rheumatology, Balgrist Campus AG, Lengghalde 5, 8008 
      Zurich, Switzerland.irina.heggli@usz.ch.
FAU - Epprecht, S
AU  - Epprecht S
FAU - Juengel, A
AU  - Juengel A
FAU - Schuepbach, R
AU  - Schuepbach R
FAU - Farshad-Amacker, N
AU  - Farshad-Amacker N
FAU - German, C
AU  - German C
FAU - Mengis, T
AU  - Mengis T
FAU - Herger, N
AU  - Herger N
FAU - Straumann, L
AU  - Straumann L
FAU - Baumgartner, S
AU  - Baumgartner S
FAU - Betz, M
AU  - Betz M
FAU - Spirig, J M
AU  - Spirig JM
FAU - Wanivenhaus, F
AU  - Wanivenhaus F
FAU - Ulrich, N
AU  - Ulrich N
FAU - Bellut, D
AU  - Bellut D
FAU - Brunner, F
AU  - Brunner F
FAU - Farshad, M
AU  - Farshad M
FAU - Distler, O
AU  - Distler O
FAU - Dudli, S
AU  - Dudli S
LA  - eng
GR  - U19 AR076737/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210608
PL  - United States
TA  - Eur Cell Mater
JT  - European cells & materials
JID - 100973416
RN  - 0 (Biomarkers)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/metabolism
MH  - Cell Differentiation/physiology
MH  - Extracellular Matrix/metabolism/physiology
MH  - Female
MH  - Fibrosis/metabolism/*physiopathology
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cells/metabolism/*physiology
MH  - Middle Aged
MH  - Myofibroblasts/metabolism/physiology
MH  - Phenotype
MH  - Signal Transduction/physiology
EDAT- 2021/06/09 06:00
MHDA- 2022/01/11 06:00
CRDT- 2021/06/08 12:34
PHST- 2021/06/08 12:34 [entrez]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2022/01/11 06:00 [medline]
AID - vol041a42 [pii]
AID - 10.22203/eCM.v041a42 [doi]
PST - epublish
SO  - Eur Cell Mater. 2021 Jun 8;41:648-667. doi: 10.22203/eCM.v041a42.