Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts in vitro

Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts in vitro

Author Caparbo, Valeria F. Google Scholar
Prada, Flavia Google Scholar
Silva, Clovis A. A. Google Scholar
Regio, Paula L. Google Scholar
Pereira, Rosa M. R. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract We examined the effects of polyarticular juvenile idiopathic arthritis (pJIA) serum on proliferation, differentiation, mineralization, and apoptosis of human osteoblast cells (hOb) in culture. the hOb were cultured with 10% serum from active pJIA and healthy controls (CT) and were tested for DNA synthesis, alkaline phosphatase (AP) activity, osteocalcin (OC) secretion, calcium levels, caspase 3 activity, and DNA fragmentation. None of the patients had used glucocorticoids for at least 1 month before the study, or any other drug that can affect bone mineral metabolism. Human inflammatory cytokine levels (IL-6, IL-8, IL-10, IL-1 beta, TNF-alpha, and IL-12p70) were measured in pJIA and CT sera. Low levels of AP activity was observed in pJIA cultures compared with CT cultures (67.16 +/- 53.35 vs 100.11 +/- 50.64 mu mol p-nitrophenol/h(-1) mg(-1) protein, P=0.008). There was also a significant decrease in OC secretion (9.23 +/- 5.63 vs 12.82 +/- 7.02 ng/mg protein, P=0.012) and calcium levels (0.475 +/- 0.197 vs 0.717 +/- 0.366 mmol/l, P=0.05) in pJIA hOb cultures. No difference was observed in cell proliferation (323.56 +/- 108.23 vs 328.91 +/- 88.03 dpm/mg protein, P=0.788). Osteoblasts cultured with JIA sera showed lower levels of DNA and increased fragmentation than osteoblasts cultured with CT sera. pJIA sera showed higher IL-6 values than CT (21.44 +/- 9.31 vs 3.58 +/- 2.38 pg/ml, P<0.001), but no difference was observed related to IL-8, IL-10, IL-1 beta, TNF-alpha, and IL-12p70 between pJIA and controls. This study suggests that serum from children with pJIA inhibits differentiation, mineralization and may increase apoptosis of hOb cultures, and inflammatory cytokines such as IL-6 might be a mechanism in this find. These results may represent an alternative therapeutic target for prevention and treatment of bone loss in JIA.
Keywords Apoptosis
Bone
Differentiation
Juvenile idiopathic arthritis
Mineralization
Osteoblast
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
PIBIC fellowship
Grant number FAPESP: 01/13835-6
PIBIC fellowship: 80.30.70/87.0
Date 2009-01-01
Published in Clinical Rheumatology. London: Springer London Ltd, v. 28, n. 1, p. 71-77, 2009.
ISSN 0770-3198 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 71-77
Origin http://dx.doi.org/10.1007/s10067-008-0985-y
Access rights Closed access
Type Article
Web of Science ID WOS:000261185900012
URI http://repositorio.unifesp.br/handle/11600/31156

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