Back to Search
Start Over
Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Dec 01; Vol. 195 (11), pp. 5136-48. Date of Electronic Publication: 2015 Nov 04. - Publication Year :
- 2015
-
Abstract
- Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Adipose Tissue cytology
Animals
Arthritis, Experimental pathology
Arthritis, Rheumatoid pathology
Autoimmunity immunology
B-Lymphocytes immunology
Bone and Bones immunology
Bone and Bones pathology
Cell Differentiation immunology
Cell Proliferation
Cells, Cultured
Disease Models, Animal
Female
Immune Tolerance immunology
Interleukin-17 metabolism
Interleukin-1beta metabolism
Lymphocyte Count
Male
Mice
Mice, Inbred DBA
T-Lymphocytes, Regulatory immunology
Tumor Necrosis Factor-alpha metabolism
Arthritis, Experimental immunology
Arthritis, Rheumatoid immunology
Bone Resorption immunology
Mesenchymal Stem Cells immunology
Osteoclasts immunology
RANK Ligand antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26538398
- Full Text :
- https://doi.org/10.4049/jimmunol.1500332