Abstract
Pigmented villonodular synovitis (PVNS) is a rare inflammatory articular disease sharing common characteristics with rheumatoid arthritis (RA), notably hyperplasia of the synovium due to a hyperproliferation of synoviocytes, and with cancer owing to mutations of the CSF1/M-CCSF gene. Targeting synovium hyperplasia by the local delivery of Cadmium (Cd) has been already tested in vitro and in vivo models of RA and could be applied to PVNS. PVNS and RA synoviocytes were exposed to low doses of Cd. After different culture time points, a qualitative analysis was done by microscopy and quantitative measurements of apoptosis, cell viability and IL-6 production were carried. IL-6 production by PVNS synovial tissue was also quantified after Cd treatment with or without the presence of pro-inflammatory cytokines (IL-17 + TNF). Addition of Cd induced cell death in both PVNS (1 ppm) and RA (0.1 ppm) synoviocytes, which increased with time and Cd concentrations. Cd increased the percentage of apoptotic cells and decreased cell viability and IL-6 production. In all these experiments, PVNS synoviocytes were tenfold less sensitive to Cd than RA synoviocytes. Cd decreased IL-6 production by PVNS synovial tissue and its effect was enhanced with pro-inflammatory cytokines. In summary, PVNS synoviocytes show resistance to Cd-induced cell death and decreased inflammation. Intra-articular use of Cd could represent a potential therapeutic tool in PVNS.
Highlights
Pigmented villonodular synovitis (PVNS) is a rare inflammatory articular disease sharing common characteristics with rheumatoid arthritis (RA), notably hyperplasia of the synovium due to a hyperproliferation of synoviocytes, and with cancer owing to mutations of the CSF1/M-CCSF gene
Described for the first time in 1941, pigmented villonodular synovitis (PVNS), known as tenosynovial giant cell tumor, is a rare articular disease characterized by an inflammatory synovitis with proliferation of synoviocytes and accumulation of large size monocyte-derived osteoclasts in the synovial tissue of joints[1]
The molecular changes combine a specific translocation of the monocyte colonystimulating factor 1 (M-CSF1) gene that leads to CSF1/M-CSF overexpression resulting in an accumulation of non-neoplastic monocyte-like inflammatory cells and inflammatory cytokine production as in RA
Summary
Pigmented villonodular synovitis (PVNS) is a rare inflammatory articular disease sharing common characteristics with rheumatoid arthritis (RA), notably hyperplasia of the synovium due to a hyperproliferation of synoviocytes, and with cancer owing to mutations of the CSF1/M-CCSF gene. Described for the first time in 1941, pigmented villonodular synovitis (PVNS), known as tenosynovial giant cell tumor, is a rare articular disease characterized by an inflammatory synovitis with proliferation of synoviocytes and accumulation of large size monocyte-derived osteoclasts in the synovial tissue of joints[1]. The lack of new local treatments apart from surgery creates the need to identify new options for the local treatment of arthritis In this context, targeting of stromal cells/synoviocytes with metals such as Cadmium (Cd) needs to be evaluated[11]. In preclinical studies linked to RA, the use of Cd has demonstrated the induction of massive cell death
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