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

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 n...

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Main Authors: Fang Li, Xin Li, Guiyan Liu, Chong Gao, Xiaofeng Li
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/8459281
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author Fang Li
Xin Li
Guiyan Liu
Chong Gao
Xiaofeng Li
author_facet Fang Li
Xin Li
Guiyan Liu
Chong Gao
Xiaofeng Li
author_sort Fang Li
collection DOAJ
description 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.
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spelling doaj-art-fff218cdb5d54d04a9461e507219830c2025-02-03T05:50:34ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/84592818459281Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22Fang Li0Xin Li1Guiyan Liu2Chong Gao3Xiaofeng Li4Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, ChinaEndocrine Metabolism and Immune Center, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, ChinaDepartment of Nephrology, Changzhi People’s Hospital, Changzhi 046000, ChinaDepartment of Pathology, Joint Program in Transfusion Medicine, Brigham and Women’s Hospital/Children’s Hospital Boston, Harvard Medical School, Boston, MA, USADepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, ChinaObjective. 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.http://dx.doi.org/10.1155/2019/8459281
spellingShingle Fang Li
Xin Li
Guiyan Liu
Chong Gao
Xiaofeng Li
Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22
Journal of Immunology Research
title Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22
title_full Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22
title_fullStr Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22
title_full_unstemmed Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22
title_short Bone Marrow Mesenchymal Stem Cells Decrease the Expression of RANKL in Collagen-Induced Arthritis Rats via Reducing the Levels of IL-22
title_sort bone marrow mesenchymal stem cells decrease the expression of rankl in collagen induced arthritis rats via reducing the levels of il 22
url http://dx.doi.org/10.1155/2019/8459281
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AT xinli bonemarrowmesenchymalstemcellsdecreasetheexpressionofranklincollageninducedarthritisratsviareducingthelevelsofil22
AT guiyanliu bonemarrowmesenchymalstemcellsdecreasetheexpressionofranklincollageninducedarthritisratsviareducingthelevelsofil22
AT chonggao bonemarrowmesenchymalstemcellsdecreasetheexpressionofranklincollageninducedarthritisratsviareducingthelevelsofil22
AT xiaofengli bonemarrowmesenchymalstemcellsdecreasetheexpressionofranklincollageninducedarthritisratsviareducingthelevelsofil22