Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22.

Abstract

OBJECTIVE:

To investigate the transplantation effect of bone marrow mesenchymal stem cells (MSCs) on the expression of interlukin-22 (IL-22) and RANKL in collagen-induced arthritis (CIA) rats.

METHODS:

32 CIA models were established. 16 CIA rats were transplanted with MSCs, and others were used as nontreatment CIA controls. The concentrations of IL-22 and RANKL in serum were detected by ELISA and those in synovial tissue of rats' joints by immunohistochemical staining. In addition, the expression of RANKL mRNA was measured by RT-PCR in the fibroblast-like synoviocytes (FLSs), cultured with IL-22 in vitro, which were delivered from the joints of CIA rats treated with or without MSCs.

RESULTS:

The transplantation of MSCs into CIA rats relieved the destruction of joints, measured by AI score, X-ray, and histopathology. MSCs also reduced the expression of IL-22 and RANKL in serum by ELISA (P < 0.001) and similarly in FLSs by immunohistochemical staining. In vitro, IL-22 induced significantly the expression of RANKL mRNA in cultured FLSs in a dose-dependent manner, whereas this induction was significantly reduced in FLSs derived from CIA rats transplanted with MSCs (normal controls: F = 79.33, P < 0.001; CIA controls: F = 712.72, P < 0.001; and CIA-MSC rats: F = 139.04, P < 0.001).

CONCLUSION:

Our results suggest that the transplantation of MSCs can reduce the expression of RANKL in vivo by downregulating the levels of IL-22, thereby ameliorating the degree of RA bone destruction. This study provides a theoretical basis for a potential therapy of RA with MSCs, and IL-22 and RANKL may become two new targets to treat RA.

• Authors: Fang Li, Xin Li, Guiyan Liu, Chong Gao, Xiaofeng Li
• Journal: Journal of immunology research (J Immunol Res) Vol. 2019 Pg. 8459281 ( 2019) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 31828174 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Fang Li et al.

Chemical References

• Interleukins
• RANK Ligand
• interleukin-22

Topics

• Animals
• Arthritis, Experimental (genetics, immunology, pathology, therapy)
• Female
• Fibroblasts (drug effects, immunology, pathology)
• Gene Expression Regulation
• Interleukins (antagonists & inhibitors, genetics, immunology, pharmacology)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, immunology)
• Primary Cell Culture
• RANK Ligand (antagonists & inhibitors, genetics, immunology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Synovial Membrane (immunology, pathology)
• Synoviocytes (drug effects, immunology, pathology)