J Rheum Dis 2016; 23(6): 356-362
Published online December 31, 2016
© Korean College of Rheumatology
Correspondence to : Won Park, Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon 22332, Korea. E-mail:parkwon@inha.ac.kr
This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. Methods. Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. Results. The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 μmol/well at the baseline to 752.5±671.9 μmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. Conclusion. The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.
Keywords Rheumatoid arthritis, Osteoblast, Osteoclast, Biologic therapy, Bone
J Rheum Dis 2016; 23(6): 356-362
Published online December 31, 2016 https://doi.org/10.4078/jrd.2016.23.6.356
Copyright © Korean College of Rheumatology.
Mie Jin Lim, Seong Ryul Kwon, Kyong-Hee Jung, Won Park
Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea
Correspondence to:Won Park, Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon 22332, Korea. E-mail:parkwon@inha.ac.kr
This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. Methods. Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. Results. The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 μmol/well at the baseline to 752.5±671.9 μmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. Conclusion. The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.
Keywords: Rheumatoid arthritis, Osteoblast, Osteoclast, Biologic therapy, Bone
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