Activated NF-?B in bone marrow mesenchymal stem cells from systemic lupus erythematosus patients inhibits osteogenic differentiation through downregulating Smad signaling.

ABSTRACT: 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 ?B (NF-?B) signaling was activated while the BMP/Smad pathway was repressed in BMMSCs from SLE patients. TNF activated NF-?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-?B inhibitor, to SLE-BMMSCs could partially reverse these effects. Thus, our findings have shown that the activated NF-?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.

SUBMITTER: Tang Y 

PROVIDER: S-EPMC3564481 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature