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.
Highlights
Rheumatoid arthritis (RA) is a kind of chronic autoimmune diseases, characterized by cartilage and bone destruction [1]
The expression of RANKL mRNA was measured by reverse transcription polymerase chain reaction (RT-PCR) in the fibroblast-like synoviocytes (FLSs), cultured with IL-22 in vitro, which were delivered from the joints of collagen-induced arthritis (CIA) rats treated with or without mesenchymal stem cells (MSCs)
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
Summary
Rheumatoid arthritis (RA) is a kind of chronic autoimmune diseases, characterized by cartilage and bone destruction [1]. There is no method to repair the damaged cartilage and bone, so finding a new effective treatment of RA has been a hot topic for rheumatologists. Osteoclasts, which are derived from a mononuclear phagocyte system, have been found to play a role in bone erosion and joint destruction. A relative excess of bone resorption over bone formation has been considered a major cause of osteopenia and joint destruction in RA. Osteoclasts play an indispensable role in keeping balance between bone resorption and bone formation [4]. Many researchers have attempted to delay the progression of bone destruction in RA, by finding a method to inhibit or block the osteoclast differentiation
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