The observed bone loss in patients with IBD is from either osteopenia or osteoporosis. It is estimated click here that 31�C59% of adult patients with IBD are classified as osteopenic, whereas 18�C24% are diagnosed with osteoporosis (1, 4, 13). The pathogenesis of IBDs is not fully understood, but the cytokine profiles of the patients hint at the possibility of cytokines playing a prominent role since these patients have an imbalance of proinflammatory cytokines (12, 26). Patients with IBD have increased levels in number of cytokines including IL-1, IL-6, interferon (IFN-��), and tumor necrosis factor-�� (TNF-��) (17). TNF-�� has been named the mastermind of the inflammatory response since treatment of anti-TNF-�� antibodies controls the progression of IBD and also increases bone mineral density (6, 16).

Phosphate is an important element for the body because it is essential for ATP synthesis, acid/base regulation, and the formation of nucleotides. Most importantly, it is a key component of bone. In fact, the bone matrix stores 85% of the body phosphate. Mammalian phosphate homeostasis is tightly regulated by controlling intestinal and renal epithelial transport mechanisms. In the renal proximal tubules, phosphate reabsorption is mediated by type IIa sodium-phosphate cotransporters (NaPi-IIa). Intestinal absorption of dietary phosphate is mediated by another subtype of type II NaPi cotransporters expressed on the apical membranes of enterocytes named NaPi-IIb (14, 19, 37). Enterocytes also express another NaPi cotransport protein on the basolateral membranes called NaPi-III, and this isoform most likely plays a role in cellular phosphate homeostasis (3, 9).

For intestinal phosphate absorption, however, NaPi-IIb is the most important of these cotransporters to study. Phosphate transport in the intestine has already been shown to be regulated by age (2, 36, 38), vitamin D3 (8, 11, 36), and hormones such as glucocorticoid (2) and estrogen (42). Since metabolic bone diseases like osteopenia and osteoporosis are associated with IBD, it is necessary to understand the molecular mechanisms of aberrant phosphate homeostasis in patients with IBD. Although TNF-�� has been found to affect bone density by inducing osteoclasts to erode the bone and by inhibiting osteoblasts to lay new bone matrix (35), how the state of inflammation affects the intestinal phosphate absorption is unknown.

Because of the fact that phosphate absorption is segment specific (ileum in mouse and jejuna in rat), we chose both of the animals as our in vivo model in our present studies. We aim to study the effects of inflammation on intestinal phosphate transport and ultimately bone health. MATERIALS AND METHODS Animals. Carfilzomib Six-week-old male Balb/C mice or 3-wk-old male Sprague Dawley rats were administered trinitrobenzene sulphonic acid (TNBS) in 50% ethanol (2 mg/mouse or 1 mg/rat) by an enema into the colonic lumen.