Matrix remodeling associated 7 promotes differentiation of bone marrow mesenchymal stem cells toward osteoblasts.

The matrix remodeling associated 7 (MXRA7) gene had been ill-studied and its biology remained to be discovered. Inspired by our previous findings and public datasets concerning MXRA7, we hypothesized that the MXRA7 gene might be involved in bone marrow mesenchymal stem cells (BMSCs) functions related to bone formation, which was checked by utilizing in vivo or in vitro methodologies. Micro-computed tomography of MXRA7-deficient mice demonstrated retarded osteogenesis, which was reflected by shorter femurs, lower bone mass in both trabecular and cortical bones compared with wild-type (WT) mice. Histology confirmed the osteopenia-like feature including thinner growth plates in MXRA7-deficient femurs. Immunofluorescence revealed less osteoblasts in MXRA7-deficient femurs. Polymerase chain reaction or western blot analysis showed that when WT BMSCs were induced to differentiate toward osteoblasts or adipocytes in culture, MXRA7 messenger RNA or protein levels were significantly increased alongside osteoblasts induction, but decreased upon adipocytes induction. Cultured MXRA7-deficient BMSCs showed decreased osteogenesis upon osteogenic differentiation induction as reflected by decreased calcium deposition or lower expression of genes responsible for osteogenesis. When recombinant MXRA7 proteins were supplemented in a culture of MXRA7-deficient BMSCs, osteogenesis or gene expression was fully restored. Upon osteoblast induction, the level of active ß-catenin or phospho-extracellular signal-regulated kinase in MXRA7-deficient BMSCs was decreased compared with that in WT BMSCs, and these impairments could be rescued by recombinant MXRA7 proteins. In adipogenesis induction settings, the potency of MXRA7-deficient BMSCs to differentiate into adipocytes was increased over the WT ones. In conclusion, this study demonstrated that MXRA7 influences bone formation via regulating the balance between osteogenesis and adipogenesis in BMSCs.

Selenizing Hericium erinaceus polysaccharides induces dendritic cells maturation through MAPK and NF-κB signaling pathways.

In this study, polysaccharides extracted from Hericium erinaceus were modified to obtain its nine selenium derivatives, sHEP1-sHEP9. Their structures were identified, yields and selenium contents were determined, the phenotypic and functional maturation of murine bone marrow-derived dendritic cells (DCs) and relevant mechanisms were compared taking unmodified HEP as control. The results revealed that the selenylation were successful. sHEP1, sHEP2 and sHEP8 treatment of DCs increased their surface expression of MHC-II and CD86 and indicated that sHEP1, sHEP2 and sHEP8 induced DC maturation. Furthermore, sHEP2 and sHEP8 also significantly decreased DCs endocytosis and significantly enhanced cytokine (IL-12 and IFN-γ) production. In line with TLR4 activation, sHEP2 increased the phosphorylation of ERK, p38, and JNK, and the nuclear translocation of p-c-Jun, p-CREB, and c-Fos. sHEP2 also activated NF-κB signaling, as evidenced by degradation of IκBα/ß and nuclear translocation of p65 and p50. Together, these results suggest that sHEP is a strong immunostimulant.

Effects of Selenizing Codonopsis pilosula Polysaccharide on Macrophage Modulatory Activities.

The purpose of the present study was to investigate the immune-enhancing activity of selenizing Codonopsis pilosula polysaccharide (sCPPS5) in nonspecific immune response. In in vitro experiment, the results showed that sCPPS5 could promote the phagocytic uptake, NO production, and TNF-α and IL-6 secretion of RAW264.7 cells. sCPPS5 could also strongly increase the IκB-α degradation in the cytosol and the translocation of NF-κB p65 subunit into the nucleus of RAW264.7 cells. In the vivo experiment, sCPPS5 at medium doses could significantly improve the phagocytic index of peritoneal macrophages and induce the secretion of TNF-α and IL-6. Moreover, the effect of sCPPS5 was significantly better than Codonopsis pilosula polysaccharide (CPPS). These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of CPPS in the nonspecific immune response.