Long-term tumor necrosis factor treatment induces NFκB activation and proliferation, but not osteoblastic differentiation of adipose tissue-derived mesenchymal stem cells in vitro.

The pro-inflammatory cytokine tumor necrosis factor (TNF) is well known to induce differentiation of bone matrix-resorbing osteoclasts from hematopoietic stem cells. However, the impact of TNF on differentiation of bone matrix-forming osteoblasts from mesenchymal stem cells (MSC) was only fragmentarily studied so far. Therefore, we investigated what impact long-term TNF treatment has on osteoblastic differentiation of MSC isolated from the adipose tissue (ASC) in vitro. In summary, we found continuous TNF exposure to induce the nuclear factor of kappa B pathway in ASC as well as secretion of the pro-inflammatory chemokine interleukin 8, but not the mitogen-activated protein kinase and the apoptosis pathway in ASC. Moreover, TNF neither induced nor inhibited osteoblastic differentiation of ASC, but strongly increased their proliferation rate. In that manner, pro-inflammatory conditions in vivo may generate significantly increased numbers of progenitor cells, and ASC especially, in conjunction with external stimuli, may contribute to the events of ectopic ossification observed in chronic inflammatory diseases. The substantiation of the translation of our in vitro findings to the disease context encourages further in vivo studies.