MY-1-Loaded Nano-Hydroxyapatite Accelerated Bone Regeneration by Increasing Type III Collagen Deposition in Early-Stage ECM via a Hsp47-Dependent Mechanism.

The extracellular matrix (ECM) plays a crucial part in regulating stem cell function through its distinctive mechanical and chemical effect. Therefore, it is worth studying how to activate the driving force of osteoblast cells by dynamic changing of ECM and accelerate the bone regeneration. In this research, a novel peptide MY-1 is designed and synthesized. To achieve its sustained releasing, the nano-hydroxyapatite (nHA) is chosen as the carrier of MY-1 by mixed adsorption. The results reveal that the sustainable releasing of MY-1 regulates the synthesis and secretion of ECM from rat bone marrow mesenchymal stem cells (rBMSCs), which promotes the cell migration and osteogenic differentiation in the early stage of bone regeneration. Further analyses demonstrate that MY-1 increases the expression and nuclear translocation of ß-catenin, and then upregulates the level of heat shock protein 47 (Hsp47), thereby accelerating the synthesis and secretion of type III collagen (Col III) at the early stage. Finally, the promoted rapid transformation of Col III to Col I at late stage benefits the bone regeneration. Hence, this study can provide a theoretical basis for the local application of MY-1 in bone regeneration.

NDRG2 inhibits the proliferation of breast cancer cells via regulating β-catenin expression and nuclear translocation / 中国癌症杂志

Background and purpose:Breast cancer is one of the most common malignant diseases in women and its malignant proliferation is the major cause of death. To investigate the effects of N-myc downstream regulated gene 2 (NDRG2) on proliferation of breast cancer cells by using two parallel cell lines (MCF-7 and LM-MCF-7) with different metastatic abilities.Methods:The expression level of NDRG2 in breast cancer cells was detected by Western blot. The effects of overexpressing (or down-regulating) NDRG2 on proliferation of breast cancer cells were investigat-ed by lfow cytometry. The expression and location of β-catenin were detected by Western blot and immunolfuorescence respectively. NDRG2 blocking the transcription activity of β-catenin was investigated via co-transfecting MCF-7 cells with NDRG2 siRNA and pCMV-Tcfδ (lacking the portion responsible for the protein binding to DNA).Results:The expression level of NDRG2 was negatively related to the proliferation ability of breast cancer cells. Over-expressing NDRG2 (or down-regulating) via transfecting LM-MCF-7 (or MCF-7) cells with pCMV-NDRG2 (or NDRG2 siRNA) could inhibit (or promote) cell proliferation. Interestingly, the results of Western blot, immunolfuorescence and lfow cytometry revealed that down-regulation of NDRG2 resulted from the down-regulation of β-catenin and blocking its nuclear translocation, which led to losing control of the proliferation of breast cancer cells.Conclusion:NDRG2 inhibit the proliferation of breast cancer cells via down-regulating the expression of β-catenin and blocking its nuclear translo-cation, which is signiifcant for exploring the molecular mechanism of proliferation of breast cancer cells.