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
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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