Repulsive guidance molecule b (RGMb), a glycosylphosphatidylinositol-anchored member of the RGM family, is initially identified as a co-receptor of bone morphogenetic protein (BMP) in the nervous system. The expression of RGMb is transcriptionally regulated by dorsal root ganglion 11 (DRG11), which is a transcription factor expressed in embryonic DRG and dorsal horn neurons and plays an important role in the development of sensory circuits. RGMb is involved in important physiological processes such as embryonic development, immune response, intercellular adhesion and tumorigenesis. Furthermore, RGMb is mainly involved in the regulation of RGMb–neogenin–Rho and BMP signalling pathways. The recent discovery of programmed death-ligand 2 (PD-L2)–RGMb binding reveals that the cell signalling network and functional regulation centred on RGMb are extremely complex. The latest report suggests that down-regulation of the PD-L2–RGMb pathway in the gut microbiota promotes an anti-tumour immune response, which defines a potentially effective immune strategy. However, the biological function of RGMb in a variety of human diseases has not been fully determined, and will remain an active research field. This article reviews the properties and functions of RGMb, focusing on its role under various physiological and pathological conditions.

The generation of germ cells from embryonic stem cells in vitro has current historical significance. Western blot, qPCR, immunofluorescence and flow cytometry assays were used to investigate the differences in expression levels of totipotency and specific markers for Wnt regulation and the related signalling pathways during primordial germ cell-like cell (PGCLC) induction and differentiation. During PGCLC induction, activation of WNT3a increased the expression of NANOG, SOX2 and OCT4, but Mvh, DAZL, Blimp1, TFAP2C, Gata4, SOX17, EOMES, Brachyury and PRDM1 expression levels were significantly reduced. Inhibition of the WNT signal demonstrated the opposite effect. Similarly, inhibitors of BMP and the Nodal/Activin signal were used to determine the effect of signal pathways on differentiation. CER1 affected the Wnt signal and differentiation, but the inhibitor SB only regulated differentiation. BMP–WNT–NODAL were mainly responsible for regulating differentiation. Our results provide a reliable theoretical basis and feasibility for further clinical medical research.

Recent studies have demonstrated the defocus sign-dependent, bidirectional gene expression regulation of bone morphogenetic proteins, BMP2, 4 and 7 in chick RPE. In this study, we examined the effects of imposed positive (+10 D) and negative (−10 D) lenses on the gene expression of these BMPs and BMP receptors (BMPR1A, BMPR1B, BMPR2) in chick retina and choroid after monocular lens treatment for 2 or 48 h, as indicators of the roles of retinal and choroidal BMPs and receptors in postnatal eye growth regulation. In retina, although all genes were expressed, neither +10 nor −10 D lenses, worn for either 2 or 48 h, significantly altered gene expression. In contrast, treatment-related differential gene expression was detected in the choroid for both BMPs and their receptors, although interestingly, with the +10 D lens, BMP2 was up-regulated by 156.7 ± 19.7% after 2 h, while BMPR1A was down-regulated to 82.3 ± 12.5% only after 48 h. With the −10 D lens, only the gene expression of BMPR1B was significantly altered, being up-regulated by 162.3 ± 21.2% after 48 h. Untreated birds showed no difference in expression between their two eyes, for any of the genes examined. The finding that retinal gene expression for BMP2, 4, 7 and their receptors are not affected by short-term optical defocus contrasts with previous observations of sign-dependent expression changes for the same genes in the RPE. The latter changes were also larger and more consistent in direction than the choroidal gene expression changes reported here. The interrelationship between these various changes and their biological significance for eye growth regulation are yet to be elucidated.

Using a sequential in vitro/in vivo approach, we tested the ability of botanical extracts to influence biomarkers associated with bone resorption and bone formation. Pomegranate fruit and grape seed extracts were found to exhibit anti-resorptive activity by inhibiting receptor activator of nuclear factor-κB ligand (RANKL) expression in MG-63 cells and to reduce IL-1β-stimulated calvarial 45Ca loss. A combination of pomegranate fruit and grape seed extracts were shown to be effective at inhibiting bone loss in ovariectomised rats as demonstrated by standard histomorphometry, biomechanical and bone mineral density measurements. Quercetin and licorice extract exhibited bone formation activity as measured by bone morphogenetic protein-2 (BMP-2) promoter activation, increased expression of BMP-2 mRNA and protein levels, and promotion of bone growth in cultured mouse calvariae. A combination of quercetin and licorice extract demonstrated a potential for increasing bone mineral density in an intact female rat model as compared with controls. The results from this sequential in vitro/in vivo research model yielded botanical extract formulas that demonstrate significant potential benefits for bone health.

Mg deficiency accelerates Fe accumulation in the liver, which may induce various metabolic disturbances. In the present study, we examined the gene expression of Hepcidin, a peptide hormone produced in the liver to regulate intestinal Fe absorption negatively, in Mg-deficient rats. Although liver Fe concentration was significantly higher in rats fed an Mg-deficient diet for 4 weeks than in rats fed a control diet, Hepcidin expression in the liver was comparable between the dietary groups. Previous studies revealed that Fe overload up-regulated Hepcidin expression through transcriptional activation by Fe-induced bone morphogenetic protein (Bmp) 6, a growth/differentiation factor belonging to the transforming growth factor-β family, in the liver. Mg deficiency up-regulated the expression of Bmp6 but did not affect the expression of inhibition of DNA binding 1, a sensitive Bmp-responsive gene. In addition, the expression of Bmp receptors such as activin receptor-like kinase 2 (Alk2), activin receptor type IIA (Actr2a), activin receptor type IIB (Actr2b) and Bmp type II receptor (Bmpr2) was lower in the liver of Mg-deficient rats than in that of control rats. The present study indicates that accumulation of hepatic Fe by Mg deficiency is a stimulant inducing Bmp6 expression but not Hepcidin expression by blunting Bmp signalling possibly resulting from down-regulation of the receptor expression. Unresponsive Hepcidin expression may have a role in Mg deficiency-induced changes related to increased liver Fe.