Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease

Chronic inflammation affects bone metabolism and is commonly associated with the presence of osteoporosis. Bone loss is directed by various immune mediators such as the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin 1-beta or interferon-gamma. Pre-B cell colony enhancing factor (PBEF)/nicotinamide phosphoribosyl transferase (NAMPT)/visfatin is a pleiotropic mediator acting as growth factor, cytokine and enzyme involved in energy and nicotinamide adenine dinucleotide (NAD) metabolism. PBEF/NAMPT/visfatin has been recently demonstrated to exert several pro-inflammatory functions. We studied serum levels of PBEF/NAMPT/visfatin in patients with inflammatory bowel diseases (IBD) and their relation with bone mineral density (BMD). Furthermore, we were interested whether PBEF/NAMPT/visfatin affects osteoclastogenesis and involved mediators. PBEF/NAMPT/visfatin serum levels were increased in patients with IBD, correlated positively with disease activity and negatively with BMD, especially in the lumbar spine. Osteoclast precursor cells were generated from peripheral blood mononuclear cells after stimulation with various growth factors such as macrophage colony-stimulating factor (M-CSF) and soluble ligand of receptor activator of nuclear factor kappa B (RANK). In these in vitro studies, PBEF/NAMPT/visfatin suppressed osteoclastogenesis and inhibited the differentiation of osteoclast precursors into tartrate-resistant acid phosphatase positive multinucleated cells. These effects were paralleled by the suppression of the osteoclast typical markers RANK, nuclear factor of activated T-cells c1 (NFATc1) and cathepsin-K. This is the first report demonstrating a potential role for this important cytokine/enzyme in inflammation-related bone disease.