Fetal Immunomodulatory Environment Following Cartilage Injury-The Key to CARTILAGE Regeneration?
Acute-Phase Proteins
/ metabolism
Animals
Cartilage, Articular
/ growth & development
Cell- and Tissue-Based Therapy
/ methods
Cells, Cultured
Fetus
/ physiology
Macrophages
/ cytology
Mesenchymal Stem Cells
/ metabolism
Neutrophils
/ cytology
Osteoarthritis
/ pathology
Regeneration
/ physiology
Sheep
Synovial Membrane
/ cytology
cartilage
fetal
immunomodulation
inflammation
macrophage
neutrophil
regeneration
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Nov 2021
30 Nov 2021
Historique:
received:
05
11
2021
revised:
27
11
2021
accepted:
28
11
2021
entrez:
10
12
2021
pubmed:
11
12
2021
medline:
21
12
2021
Statut:
epublish
Résumé
Fetal cartilage fully regenerates following injury, while in adult mammals cartilage injury leads to osteoarthritis (OA). Thus, in this study, we compared the in vivo injury response of fetal and adult ovine articular cartilage histologically and proteomically to identify key factors of fetal regeneration. In addition, we compared the secretome of fetal ovine mesenchymal stem cells (MSCs) in vitro with injured fetal cartilage to identify potential MSC-derived therapeutic factors. Cartilage injury caused massive cellular changes in the synovial membrane, with macrophages dominating the fetal, and neutrophils the adult, synovial cellular infiltrate. Correspondingly, proteomics revealed differential regulation of pro- and anti-inflammatory mediators and growth-factors between adult and fetal joints. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult compared to fetal cartilage following injury. In contrast, several immunomodulating proteins and growth factors were expressed significantly higher in the fetus than the adult. Comparison of the in vitro MSCs proteome with the in vivo fetal regenerative signature revealed shared upregulation of 17 proteins, suggesting their therapeutic potential. Biomimicry of the fetal paracrine signature to reprogram macrophages and modulate inflammation could be an important future research direction for developing novel therapeutics.
Identifiants
pubmed: 34884768
pii: ijms222312969
doi: 10.3390/ijms222312969
pmc: PMC8657887
pii:
doi:
Substances chimiques
Acute-Phase Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Research Promotion Agency
ID : 7269695
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