Krstić J, Mojsilović S, Mojsilović SS, Santibanez JF. Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation. World J Stem Cells 2021; 13(11): 1696-1713 [PMID: 34909118 DOI: 10.4252/wjsc.v13.i11.1696]
Corresponding Author of This Article
Juan F Santibanez, PhD, Professor, Research Scientist, Group for Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr. Subotića 4, Belgrade 11000, Serbia. jfsantibanez@imi.bg.ac.rs
Research Domain of This Article
Cell Biology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Nov 26, 2021; 13(11): 1696-1713 Published online Nov 26, 2021. doi: 10.4252/wjsc.v13.i11.1696
Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation
Jelena Krstić, Slavko Mojsilović, Sonja S Mojsilović, Juan F Santibanez
Jelena Krstić, Gottfried Schatz Research Center, Medical University of Graz, Graz 8010, Austria
Slavko Mojsilović, Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade 11129, Serbia
Sonja S Mojsilović, Group for Immunology, Institute for Medical Research, National Institute of Republic of Serbia, Belgrade 11129, Serbia
Juan F Santibanez, Group for Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
Juan F Santibanez, Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O’Higgins, Chile 8370993, Chile
Author contributions: Santibanez JF designed the article; Santibanez JF and Mojsilović SS collected literature data; Santibanez JF,Krstić J and Mojsilović S wrote the paper.
Supported byMinistry of Education, Science and Technological Development of Serbia, No. 451-03-9/2021-14/200015; and Oesterreichische Nationalbank (Austrian Central Bank, Anniversary Fund), No. 18517 (to Krstić J).
Conflict-of-interest statement: The authors declare no potential conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Juan F Santibanez, PhD, Professor, Research Scientist, Group for Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr. Subotića 4, Belgrade 11000, Serbia. jfsantibanez@imi.bg.ac.rs
Received: March 5, 2021 Peer-review started: March 5, 2021 First decision: May 5, 2021 Revised: May 14, 2021 Accepted: October 18, 2021 Article in press: October 18, 2021 Published online: November 26, 2021 Processing time: 264 Days and 22.9 Hours
Abstract
Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury. The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response. Interleukin (IL)-17A, produced in the early phase of inflammation, influences the fate of osteoprogenitors. Due to their inherent capacity to differentiate into osteoblasts, mesenchymal stem/stromal cells (MSCs) contribute to bone healing and regeneration. This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs. The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described. To this end, divergent information exists about the capacity of IL-17A to regulate MSCs’ osteogenic fate, depending on the tissue context and target cell type, along with contradictory findings in the same cell types. Therefore, we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17, which may help in the understanding of IL-17A function in bone repair and regeneration.
Core Tip: The immune system closely interacts with the bone system in health and disease. Inflammation plays a strategic role in bone homeostasis and turnover. A proinflammatory cytokine interleukin-17 (IL-17) is produced in high amounts after bone damage and can influence mesenchymal stem cells’ fate toward early osteoprogenitor cells, either as a pro-osteogenic or an anti-osteogenic factor. Although these divergent IL-17 roles in bone formation are still not well understood, different conditions of the local microenvironment, the extent of inflammation, and the specific nature and stage of osteoprogenitor cells can influence the response to this cytokine, affecting the final cell differentiation outcome.
