Journal
STEM CELLS AND DEVELOPMENT
Volume 22, Issue 4, Pages 668-678Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2012.0226
Keywords
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Funding
- Major International (Regional) Joint Research Project [81120108021]
- National Natural Science Foundation of China [30972736, 81202358]
- Jiangsu Province Natural Science Foundation [BK2009034]
- Jiangsu Province Kejiao Xingwei Program
- Chinese National 115 Supporting Program [2008BAI 59B02]
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Osteoporosis in patients with systemic lupus erythematosus (SLE) is thought to be the result of accelerated osteoclastogenesis induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF). However, the molecular mechanisms involved in the osteoblastogenesis in SLE patients are not fully understood. We investigated the bone morphogenetic protein-2 (BMP-2)-induced osteoblastic capacity of bone marrow-derived mesenchymal stem cells (BMMSCs) from SLE patients and the TNF signaling system in determining BMP-2-induced regulatory pathways. It showed that the capacity of osteogenic differentiation of BMMSCs from SLE patients was reduced compared with that from healthy controls. The nuclear factor kappa B (NF-kappa B) signaling was activated while the BMP/Smad pathway was repressed in BMMSCs from SLE patients. TNF activated NF-kappa B pathway and inhibited the phosphorylation of Smad 1/5/8 and BMP-2-induced osteoblastic differentiation in BMMSCs from normal controls, while addition of pyrollidine dithiocarbamate (PDTC), an NF-kappa B inhibitor, to SLE-BMMSCs could partially reverse these effects. Thus, our findings have shown that the activated NF-kappa B pathway in SLE-BMMSCs inhibits the BMP-2-induced osteoblastic differentiation through BMP/Smad signaling pathway, suggesting that the impaired osteoblastic differentiation may participate in the pathology of osteoporosis in SLE patients.
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