Bone marrow mesenchymal stem cells improve bone erosion in collagen-induced arthritis by inhibiting osteoclasia-related factors and differentiating into chondrocytes
Autor: | Liyun Zhang, Jingjing Fan, Jian Han, Jinfang Gao, Jianwen Hou, Dan Ma, Limin Ren, G Zhang, Ke Xu |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
musculoskeletal diseases Pathology medicine.medical_specialty Medicine (miscellaneous) Arthritis Inflammation Bone destruction Biochemistry Genetics and Molecular Biology (miscellaneous) Bone marrow-derived mesenchymal stem cells lcsh:Biochemistry 03 medical and health sciences Chondrocytes 0302 clinical medicine medicine Animals Green fluorescent protein lcsh:QD415-436 Rats Wistar Rheumatoid arthritis Tissue repair RANKL/OPG lcsh:R5-920 biology Chemistry Research Cartilage RANK Ligand Synovial Membrane Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology medicine.disease Arthritis Experimental Rats Transplantation 030104 developmental biology medicine.anatomical_structure RANKL 030220 oncology & carcinogenesis biology.protein Molecular Medicine Chemokines Synovial membrane Stem cell medicine.symptom lcsh:Medicine (General) |
Zdroj: | Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-14 (2020) Stem Cell Research & Therapy |
ISSN: | 1757-6512 |
Popis: | Background Rheumatoid arthritis (RA) is characterized by joint inflammation and damage to the cartilage and bone in collagen-induced arthritis (CIA). Mesenchymal stem cells (MSCs) can improve articular symptoms and reduce bone erosion in CIA rats; however, the underlying mechanism remains unknown. This study aimed to investigate the mechanism underlying MSC-induced improvement of bone destruction in CIA. Methods Wistar rats were divided into a normal group, CIA control group, MTX intervention group, and BMSC intervention group, each comprising 8 rats. Serum RANKL, OPG, and CXCL10 levels of all groups were determined via flow cytometry after 42 days of interventions. RANKL, OPG, TRAF6, CXCL10, and CXCR3 were detected on the synovial membrane via immunohistochemistry, and their relative mRNA levels were determined via RT-PCR analysis. BMSCs were labeled with GFP and administered to CIA rats via the tail vein. At different time points, the distribution of implanted GFP-MSCs in synovial tissues was observed using a fluorescence microscope, and the potential of GFP-MSCs to differentiate into chondrocytes was assessed via immunofluorescence analysis. Results BMSC transplantation improved joint inflammation and inhibited bone destruction in CIA rats. BMSCs inhibited the expression of serum CXCL10 and CXCL10 and CXCR3 expression at the synovial membrane. Moreover, protein and mRNA expression analyses revealed that BMSCs potentially regulated RANKL/OPG expression levels in the serum and synovial tissue. Upon implantation into CIA rats, GFP-MSCs were traced in the joints. GFP-positive cells were observed in the cartilage tissue from day 11 and until 42 days after transplantation. Anti-type II collagen/GFP double-positive cells were observed in the articular cartilage (especially damaged cartilage) upon immunofluorescence staining of anti-type II collagen. Conclusions BMSCs improve bone destruction in CIA by inhibiting the CXCL10/CXCR3 chemotactic axis, regulating the RANKL/OPG ratio, and directly differentiating into chondrocytes. |
Databáze: | OpenAIRE |
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