Hence, functional analyses will ultimately be required to definitively appreciate the mechanisms of TLR5/flagellin dimerization. Our results would indicate that on the whole, greater functional activity of the TLR5 variant rs5744174 is a risk factor for CD in children. Reasons for this remain speculative, but could include differences in recruitment of Th17 cells or dendritic cells to the intestinal lamina propria, leading to altered inflammatory tone. Our conclusions are limited by the need to use a non-intestinal cell line for functional studies, since human intestinal epithelial cells and leukocytes express native TLR5. Testing of a large cohort of volunteers with both SNPs of TLR5 at residue 616 would be required to draw conclusions about functional differences in flagellin response, because of naturally occurring polymorphisms in other inflammatory genes involved in chemokine and cytokine production. However, these future important predict precisely prognosis therapeutic effect studies could provide interesting information to guide new diagnostic or therapeutic interventions for pediatric CD. It is a public health threat due to the potentially disastrous results and high cumulative rate of fractures. It is estimated that more than 
100 million people worldwide are at risk for the disorder and fracture rates seem to be rising ceaselessly. Osteoporosis is mainly caused by an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. A number of medicines have been developed to treat osteoporosis, mainly including bone resorption inhibitors, which prevent excessive bone loss by reducing the osteoclast formation and activity; bone formation accelerators, which increase bone mineral density and bone mass by stimulating the osteoblast activity; bone mineralization drugs, which stimulate new bone mineralization. NUCB21�C83 is also called nesfatin-1. It has recently been identified as a satiety molecule associated with melanocortin signaling system detectable in central neurons as well as an anti-hyperglycemic peptide when it is given intravenously. NUCB21�C83 was also reported to have a role in the response to stress and mediation of anxiety- and/or fear-related behaviors in rats. The expression of NUCB21�C83 was induced by troglitazone, an activator of peroxisome proliferator-activated receptor-c. The activation of PPAR-c was recognized to cause loss of bone. Therefore, we have curiously examined the effect of NUCB1�C83 on bone metabolism. Since ovariectomized rat is a classic animal model for postmenopausal osteoporosis, we have intravenously injected NUCB21�C83 once a day to OVX rats continuously for two months to observe the changes in bone mineral density. In addition, we have also evaluated both the promoting effect of NUCB21�C83 on osteoblastogenesis in the mouse MC3T3-E1 preosteoblastic cell line and its inhibitory effect on osteoclastogenesis in murine RAW 264.7 macrophages, as well as its presence in osteoblasts and osteoclasts. The nucleobindins, NUCB1 and NUCB2, are homologous calcium and DNA binding proteins. It was reported that secreted extracellular NUCB1 might contribute in modulating the matrix maturation in bone with unknown mechanisms. NUCB21�C83 was originally identified as an anorexigenic factor in hypothalamus which was recently reported to be anti-hyperglycemic. However, it has not been reported to affect bone metabolism. In our experiments, the intravenous administration of NUCB21�C83 was found for the first time to increase BMD of femora and lumbar vertebrae in OVX rats. Mouse MC3T3-E1 preosteoblastic cell line was derived from calvaria of newborn mice. It has been widely applied in the investigation of mechanism underlying osteoblast differentiation as it epitomizes osteogenic differentiation and maturation in vitro. ALP is a representative marker for osteoblastic differentiation.