Osteocytes are the most abundant osteoblast lineage cells within the bone matrix. They respond to mechanical stimulation and can participate in the release of regulatory proteins that can modulate the activity of other bone cells. We hypothesize that neuropeptide Y (NPY), a neurotransmitter with regulatory functions in bone formation, is produced by osteocytes and can affect osteoblast activity. To study the expression of NPY by the osteoblast lineage cells, we utilized transgenic mouse models in which we can identify and isolate populations of osteoblasts and osteocytes. The Col2.3GFP transgene is active in osteoblasts and osteocytes, while the DMP1 promoter drives green fluorescent protein (GFP) expression in osteocytes. Real-time PCR analysis of RNA from the isolated populations of cells derived from neonatal calvaria showed higher NPY mRNA in the preosteocytes/ osteocytes fraction compared to osteoblasts. NPY immunostaining confirmed the strong expression of NPY in osteocytes (DMP1GFP + ), and lower levels in osteoblasts. In addition, the presence of NPY receptor Y1 mRNA was detected in cavaria and long bone, as well as in primary calvarial osteoblast cultures, whereas Y2 mRNA was restricted to the brain. Furthermore, NPY expression was reduced by 30-40% in primary calvarial cultures when subjected to fluid shear stress. In addition, treatment of mouse calvarial osteoblasts with exogenous NPY showed a reduction in the levels of intracellular cAMP and markers of osteoblast differentiation (osteocalcin, BSP, and DMP1). These results highlight the potential regulation of osteoblast lineage differentiation by local NPY signaling. KeywordsNeuropeptide Y; Osteocytes; Osteoblasts; GFP; Bone Neuropeptide Y (NPY) is a 36-amino acid polypeptide that belongs to the larger family of neuropeptides, which also includes the pancreatic polypeptide and the peptide YY Allen et al., 1992]. NPY signals through a class of receptors known as Y receptors, members of the G-protein-coupled receptors [Lemos et al., 1997;Raimondi et al., 2002]. The Y receptor system consists of five Y receptors; Y1, Y2, Y4, Y5, and Y6 (which is present only in the mouse). NPY is highly expressed in the hypothalamus, and its receptors Y1, Y2, and Y5 are found in the central nervous system, including the hypothalamus [Sar et al., 1990;Parker and Herzog, 1999].Functionally, NPY is a potent orexigenic peptide; its expression is up-regulated in the hypothalamus of experimental diabetic rats la Fleur et al., 2003]. NPY acts through the Y2 receptor in the hypothalamus to centrally regulate bone mass [Baldock et al., 2002]. This observation was reinforced using germline deletion of Y2 or Y1 receptors in mice, resulting in a higher trabecular bone volume and elevated cortical bone mass [Baldock et al., 2005]. Moreover, targeted deletion of Y2 in the hypothalamus revealed an increased bone volume comparable to the effect of germ line deletion of Y1 or Y2 in mice, thus confirming the Y2-mediated central regulation of bone mass [Baldock et al., 2005]. In...

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Loss of apoptotic Bax due to microsatellite mutation contributes to tumor development and chemoresistance. Recently, a Bax microsatellite mutation was uncovered in combination with a specific alternative splicing event that could generate a unique Bax isoform (BaxD2) in otherwise Bax-negative cells. Like the prototype Baxa, BaxD2 is a potent proapoptotic molecule. However, the proapoptotic mechanism and therapeutic implication of BaxD2 remain elusive. Here, the isolation and analysis of isogenic subcell lines are described that represent different Bax microsatellite statuses from colorectal cancer. Colon cancer cells harboring Bax microsatellite G7/G7 alleles are capable of producing low levels of endogenous BaxD2 transcripts and proteins. Interestingly, BaxD2-positive cells are selectively sensitive to a subgroup of chemotherapeutics compared with BaxD2-negative cells. Unlike other Bax isoforms, BaxD2 recruits caspase-8 into the proximity for activation, and the latter, in turn, activates caspase-3 and apoptosis independent of the mitochondrial pathway. These data suggest that the expression of BaxD2 may provide alternative apoptotic and chemotherapeutic advantages for Bax-negative tumors.

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Taken together, sensitive scalp showed disrupted barrier function, abnormal sebum amount and composition, as well as perturbed microbiome, which might be the direct cause. Products targeting these features could be helpful for the treatment of sensitive scalp.