Rac1, an important Rho GTPase that regulates the actin cytoskeleton, has long been suggested to participate in acetylcholine receptor (AChR) clustering at the postsynaptic neuromuscular junction. However, how Rac1 is regulated and how it influences AChR clusters have remained unexplored. This study shows that breaking the balance of Rac1 regulation, by either increasing or decreasing its activity, led to impaired formation and maintenance of AChR clusters. By manipulating Rac1 activity at different stages of AChR clustering in cultured myotubes, we show that Rac1 activation was required for the initial formation of AChR clusters, but its persistent activation led to AChR destabilization, and uncontrolled hyperactivation of Rac1 even caused excessive myotube fusion. Both AChR dispersal and myotube fusion induced by Rac1 were dependent on its downstream effector Pak1. Two Rac1 GAPs and six Rac1 GEFs were screened and found to be important for normal AChR clustering. This study reveals that, although general Rac1 activity remains at low levels during terminal differentiation of myotubes and AChR cluster maintenance, tightly regulated Rac1 activity controls normal AChR clustering.

The phytochemical investigation of the extract from the rhizomes of Polygonum amplexicaule led to the isolation of thirty compounds, including a new flavanone. The proliferation, differentiation, and mineralizaton activity were tested.

Background — Long non-coding RNAs (lncRNAs) play a crucial role in bone growth and skeletal development. Ribonuclease (RNase) for mitochondrial RNA processing, commonly known as RMRP, is a small nucleolar ribonucleoprotein particle composed of RMRP lncRNA (lncRNA RMRP) and several protein subunits. Specifically, mutations in lncRNA RMRP are associated with cartilage-hair hypoplasia and skeletal developmental disorders in humans. For instance, mutations in lncRNA RMRP are observed in individuals with severe dwarfism, thus suggesting that RMRP functions in both chondrogenic and osteogenic processes. Results of a previous study have identified a potential role of RMRP in chondrogenic differentiation in mouse cell lines. However, the specific functions of RMRP in osteogenic processes remain unclear. Methods — In the present study, RMRP expression was altered in murine bone marrow derived mesenchymal stem cells (BMSCs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), cell counting, apoptosis and mineralization assays were used to investigate the effects of RMRP on BMSCs, osteoblasts and osteogenic differentiation. Results — The results of the present study showed that RMRP expression was up-regulated in BMSCs and down-regulated during apoptosis. The RMRP knockdown resulted in decreased proliferation and viability of BMSCs and increased apoptosis. In addition, the RMRP knockdown increased osteoblast differentiation of BMSCs and affected the mineralization of osteoblastic cells. Conclusion — The results of the present study indicated that RMRP may play a role in BMSCs, osteoblastic cells and osteogenic differentiation process. Therefore, the present study may provide a new theoretical basis for the role of RMRP in skeletal development.