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Volume 22
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10.3390/ijms222312969
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Article

Fetal Immunomodulatory Environment Following Cartilage Injury—The Key to CARTILAGE Regeneration?

by
Iris Ribitsch
1,
Andrea Bileck
2,
Monika Egerbacher
3,
Simone Gabner
4,
Rupert L. Mayer
2,
Lukas Janker
2,
Christopher Gerner
2,* and
Florien Jenner
1,*
1
VETERM, Equine Surgery Unit, Department of Companion Animals and Horses, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
2
Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria
3
Administrative Unit Veterinary Medicine, UMIT—Private University for Health Sciences, Medical Informatics and Technology GmbH, 6060 Hall in Tirol, Austria
4
Histology & Embryology, Department of Pathobiology, University of Veterinary Medicine, 1210 Vienna, Austria
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(23), 12969; https://doi.org/10.3390/ijms222312969
Submission received: 5 November 2021 / Revised: 27 November 2021 / Accepted: 28 November 2021 / Published: 30 November 2021
(This article belongs to the Special Issue Inflammation, Metabolism and Molecular Changes in Tissue Repair and Regeneration)
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Abstract

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.
Keywords: cartilage; regeneration; inflammation; immunomodulation; macrophage; neutrophil; fetal cartilage; regeneration; inflammation; immunomodulation; macrophage; neutrophil; fetal

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MDPI and ACS Style

Ribitsch, I.; Bileck, A.; Egerbacher, M.; Gabner, S.; Mayer, R.L.; Janker, L.; Gerner, C.; Jenner, F. Fetal Immunomodulatory Environment Following Cartilage Injury—The Key to CARTILAGE Regeneration? Int. J. Mol. Sci. 2021, 22, 12969. https://doi.org/10.3390/ijms222312969

AMA Style

Ribitsch I, Bileck A, Egerbacher M, Gabner S, Mayer RL, Janker L, Gerner C, Jenner F. Fetal Immunomodulatory Environment Following Cartilage Injury—The Key to CARTILAGE Regeneration? International Journal of Molecular Sciences. 2021; 22(23):12969. https://doi.org/10.3390/ijms222312969

Chicago/Turabian Style

Ribitsch, Iris, Andrea Bileck, Monika Egerbacher, Simone Gabner, Rupert L. Mayer, Lukas Janker, Christopher Gerner, and Florien Jenner. 2021. "Fetal Immunomodulatory Environment Following Cartilage Injury—The Key to CARTILAGE Regeneration?" International Journal of Molecular Sciences 22, no. 23: 12969. https://doi.org/10.3390/ijms222312969

APA Style

Ribitsch, I., Bileck, A., Egerbacher, M., Gabner, S., Mayer, R. L., Janker, L., Gerner, C., & Jenner, F. (2021). Fetal Immunomodulatory Environment Following Cartilage Injury—The Key to CARTILAGE Regeneration? International Journal of Molecular Sciences, 22(23), 12969. https://doi.org/10.3390/ijms222312969

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