Abstract
In contrast to the significant advances in our understanding of the mesenchymal stem cell (MSC) populations in bone marrow (BM), little is known about the MSCs that are resident in the synovial joint and their possible roles in the tissue homeostasis, chronic inflammation as well as in repair. Neural crest is a transient embryonic structure, generating multipotential MSC capable of migrating along peripheral nerves and blood vessels to colonize most tissue types. In adult, these MSC can provide functional stromal support as a stem cell niche for lymphocyte progenitors for instance in the BM and the thymus. Critically, MSC have major immunoregulatory activities to control adverse inflammation and infection. These MSC will remain associated to vessels (perivascular (p) MSC) and their unique expression of markers such as myelin P0 and transcription factors (e.g. Gli1 and FoxD1) has been instrumental to develop transgenic mice to trace the fate of these cells in health and disease conditions. Intriguingly, recent investigations of chronic inflammatory diseases argue for an emerging role of pMSC in several pathological processes. In response to tissue injuries and with the release of host cell debris (e.g. alarmins), pMSC can detach from vessels and proliferate to give rise to either lipofibroblasts, osteoblasts involved in the ossification of arteries and myofibroblasts contributing to fibrosis. This review will discuss currently available data that suggest a role of pMSC in tissue homeostasis and pathogenesis of the synovial tissue and joints.
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Abbreviations
- alpha SMA:
-
Alpha smooth muscle actin cell marker
- ANG-1:
-
Angiopoitein-1
- BM:
-
Bone marrow
- BMPs:
-
Bone morphogenic proteins
- CAIA:
-
Collagen antibody-induced arthritis
- CDH-11:
-
Cadherin-11
- CIA:
-
Collagen-induced arthritis
- CKD:
-
Chronic kidney disease
- CSCs:
-
Cancer stem cells
- CSPG4:
-
Chondroitin sulfate proteoglycan 4
- CXCL12:
-
CXC chemokine ligand 12
- CXCL4:
-
CXC chemokine ligand 4
- DAMPS:
-
Danger-associated molecular patterns
- DCs:
-
Dendritic cells
- ECM:
-
Extracellular matrix
- EMT:
-
Epithelial mesenchymal transition
- FAP:
-
Fibroblast activation protein
- FGF:
-
Fibroblast growth factors
- FGFR:
-
Fibroblast growth factor receptor
- FLS:
-
Fibroblast-like synoviocytes
- FPR2:
-
N-formyl peptide receptor
- FZD:
-
Frizzled receptor
- GDF-5:
-
Growth and differentiation factor-5
- GFAP:
-
Glial fibrillary acidic protein
- Gli1:
-
Glioma-associated oncogene homolog 1
- gMSC:
-
Glial mesenchymal stem cell
- HMGB1:
-
High mobility group B 1
- HpSC:
-
Hepatic stellate cells
- HSC:
-
Hematopoietic stem cells
- HSP:
-
Heat shock protein
- IPF:
-
Idiopathic pulmonary fibrosis
- LEPR:
-
Leptin Receptor
- MIF:
-
Macrophage migration inhibitory factor
- MSC:
-
Mesenchymal stem cell
- Myh11:
-
Myosin heavy chain 11
- NC:
-
Neural crest
- NC-MSC:
-
Neural crest derived mesenchymal stem cell
- NG2:
-
Neuron glial antigen 2
- NK:
-
Natural killer
- OA:
-
Osteoarthritis
- P0:
-
Myelin P zero protein
- PAMPS:
-
Pathogen-associated molecular patterns
- PDGFR:
-
Platelet-derived growth factor receptor
- PRR:
-
Pathogen recognition receptors
- Ptc:
-
Patched
- RA:
-
Rheumatoid arthritis
- SCF:
-
Stem cell factor
- SDF1-α:
-
Stromal differentiation factor 1 alpha
- Shh:
-
Sonic hedgehog
- Smo:
-
Smoothened
- TEM1:
-
Tumor endothelial marker
- TGF-β:
-
transforming growth factor b
- TLRs:
-
Toll-like receptors
- VCAM:
-
Vascular endothelial cell adhesion molecule
- VEGF:
-
Vascular endothelial growth factor
- Wnt:
-
Wingless-type MMTV integration site
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The authors thank Dr. A Williams from the rheumatology department at Cardiff University.
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Authors (P Guiraud) (P Gasque), has received funding from Conseil Régional de la Réunion (GURDTI-2017-1198-0002583, Viropam) (Convention 20192211–0022768, EPIGEN).
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The work included here did not involve animals. The biopsy sample of human synovial tissue used to generate the illustration in Fig. 3 was consented for and used in accordance with the ethical standards of the institutional (Cardiff Medical school, UK) and with the 1964 Helsinki declaration and its later amendments. Thus, synovial tissues were kindly obtained from Dr. Anwen S. Williams (Rheumatology department, Cardiff University and collected from diseased joints of OA and RA patients during routine surgical intervention. Ethical approval was granted by the Bro Taf Health Authority (LREC 02/4692).
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Bedoui, Y., Lebeau, G., Guillot, X. et al. Emerging Roles of Perivascular Mesenchymal Stem Cells in Synovial Joint Inflammation. J Neuroimmune Pharmacol 15, 838–851 (2020). https://doi.org/10.1007/s11481-020-09958-z
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DOI: https://doi.org/10.1007/s11481-020-09958-z