Background/Purpose: A disintegrin and metalloprotease family proteins (ADAMs) have been reported to be involved in a number of inflammatory conditions. We have previously reported a disintegrin and metalloprotease- 17 (ADAM-17) is expressed in rheumatoid arthritis (RA) synovial fluids and synovial tissues, and is increased compared to osteoarthritis (OA) synovial fluids. Cells involved in bone formation express a variety of cytokines and osteoblasts appear to be major regulators of bone remodeling in RA. The association between ADAM-17 expression and osteoblasts is unclear. Here, we examine the expression of ADAM-17 in RA osteoblasts.

Methods: RA human osteoblasts (HOB) isolated from femora of RA patients were incubated. RA-HOB were stimulated with 25ng/ml tumor necrosis factor (TNF)-α at 4 hours, and messanger RNA (mRNA) was collected. ADAM-17 mRNA expression was examined using quantitative polymerase chain reaction (qPCR). To examine the expression of ADAM-17 in TNF-α stimulated RA-HOB conditioned medium, RA-HOB were stimulated with 0.25 ng/ml, 2.5 ng/ml and 25 ng/ml TNF-α at 24 hours and measured using enzyme linked immunosorbent assay (ELISA). To determine ADAM-17 expression in RA-HOB lysate, western brotting (WB) was also performed. Finally, to confirm the presence of ADAM-17 on RA osteoblasts, immunostaining was performed.

Results: ADAM-17 was expressed in TNF-α stimulated RA-HOBconditioned medium which was significantly higher compared to non-stimulated (NS) RA-HOB conditioned medium (mean ± SEM; 171 ± 4 pg/ml and 310 ± 21 pg/ml , respectively , p<0.05). Furthermore TNF-α was induced dose-dependent secretion of ADAM-17 levels from RA-HOB (mean±SEM; NS: 171 ± 4 pg/ml , TNF-α 0.25 ng/ml: 255 ± 15 pg/ml, TNF-α 2.5ng/ml: 234 ± 7 pg/ml, TNF-α 25 ng/ml: 310 ± 21 pg/ml, p<0.05). We found that ADAM-17 mRNA in TNF-α stimulated RA-HOB was 70 times elevated compared with in non-stimulated RA-HOB (p<0.05). Additionally, we also found that ADAM-17 expression on RA-HOB was inducible by TNF-α by using immunostaining and WB.

Conclusion: We have reported that ADAM-17 is involved in angiogenesis in synovial tissue of RA. In this study, we showed the expression of ADAM-17 in RA osteoblasts, suggesting the possibility that it plays an important role in bone destruction in inflammatory desease such as RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-disintegrin-and-metalloprotease-17-is-overexpressed-on-rheumatoid-arthritis-osteoblasts-and-is-regulated-with-tnf-%ce%b1-stimulation/