Session Title: Biology and Pathology of Bone and Joint - Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA). GMSCs have been demonstrated to suppress T cell responses and suppress the progress of experimental collagen induced arthritis model. This study aims to determine whether GMSCs also directly suppress osteoclastogenesis and bone erosion in collagen induced arthritis (CIA).
Methods: Osteoclasts were induced from bone-marrow cells with RANKL and M-CSF stimulation, and assessed with tartrate-resistant acid phosphatase (TRAP) staining. For human cells, osteoclasts were induced from human CD14+cells. GMSCs were isolated from the volunteer donors and were generated understand a standard protocol. GMSCs were added to cultures with different ratios with BM cells. Transwell, antibody or inhibitors blockade experiments were performed to define the mechanisms of action. NF-κB activation as well as RANKL expression was determined by western blot and qRT-PCR. 2×106 GMSCs or fibroblast cells were adoptively transferred to DBA1/J mice on day 14 after immunization with CII/CFA. CIA onset and severity were monitored, osteoclast expression and distribution in CIA model was analyzed by TRAP stain, and bone erosion was examined by micro CT scan.
Results: GMSCs but not fibroblast cells markedly suppressed osteoclastogenesis in vitro for human and mice. GMSCs injected after immunization and before of onset of CIA significantly suppressed disease development. Treatment with GMSCs dramatically decreased the levels of NF-κB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. Blockade of CD73 signal significantly revised the effect of GMSCs on osteoclast formation and bone erosion.
Conclusion: We demonstrate that GMSCs dramatically and directly inhibited NF-kB- and RANKL-mediated osteoclast formation, as well as bone erosion in CIA. Manipulation of GMSCs may have therapeutic effects on rheumatoid arthritis and other bone erosion related diseases.
To cite this abstract in AMA style:Zheng Y, Wang J, Olsen NJ, Rong L, Zheng SG. Gingival Tissue-Derived MSC Cells (GMSC) Suppress Osteoclastogenesis and Bone Erosion in Collagen-Induced Arthritis Thought CD73 Signal Pathway [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/gingival-tissue-derived-msc-cells-gmsc-suppress-osteoclastogenesis-and-bone-erosion-in-collagen-induced-arthritis-thought-cd73-signal-pathway/. Accessed June 3, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gingival-tissue-derived-msc-cells-gmsc-suppress-osteoclastogenesis-and-bone-erosion-in-collagen-induced-arthritis-thought-cd73-signal-pathway/