ABSTRACT
AMP-activated protein kinase (AMPK) is a typical sensor of intracellular energy metabolism. Our previous study revealed the role of activated AMPK in the suppression of osteogenic differentiation and traumatic heterotopic ossification, but the underlying mechanism remains poorly understood. The E3 ubiquitin ligase Smurf1 is a crucial regulator of osteogenic differentiation and bone formation. We report here that Smurf1 is primarily SUMOylated at a C-terminal lysine residue (K324), which enhances its activity, facilitating ALK2 proteolysis and subsequent bone morphogenetic protein (BMP) signaling pathway inhibition. Furthermore, SUMOylation of the SUMO E3 ligase PIAS3 and Smurf1 SUMOylation was suppressed during the osteogenic differentiation and traumatic heterotopic ossification. More importantly, we found that AMPK activation enhances the SUMOylation of Smurf1, which is mediated by PIAS3 and increases the association between PIAS3 and AMPK. Overall, our study revealed that Smurf1 can be SUMOylated by PIAS3, Furthermore, Smurf1 SUMOylation mediates osteogenic differentiation and traumatic heterotopic ossification through suppression of the BMP signaling pathway. This study revealed that promotion of Smurf1 SUMOylation by AMPK activation may be implicated in traumatic heterotopic ossification treatment.
Subject(s)
AMP-Activated Protein Kinases , Cell Differentiation , Ossification, Heterotopic , Osteogenesis , Protein Inhibitors of Activated STAT , Sumoylation , Ubiquitin-Protein Ligases , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Protein Inhibitors of Activated STAT/metabolism , Protein Inhibitors of Activated STAT/genetics , Osteogenesis/genetics , Animals , Humans , AMP-Activated Protein Kinases/metabolism , Ossification, Heterotopic/metabolism , Ossification, Heterotopic/genetics , Ossification, Heterotopic/pathology , Signal Transduction , Mice , Molecular Chaperones/metabolism , Molecular Chaperones/genetics , HEK293 CellsABSTRACT
Hedgehog mushroom is a Hericium erinaceus associated with fagaceae and pinaceae trees in the northern hemisphere. It is still unknown whether this symbiotic relationship will affect the endophytic microbial community of the host plants. In this study, the endophytic microbial communities of different Quercus aliena tissues (root, stem, and leaf) with or without H. erinaceus partner were analyzed by bar-coded pyrosequencing. About 29,000 clean reads were obtained per sample representing 28 phyla of bacteria and 6 phyla of fungi. A total of 26,838 operational taxonomic units (OTUs) of bacteria and 4323 OTUs of fungi were observed at a 97% similarity level. Three bacterial phyla, Proteobacteria, Cyanobacteria and Bacteroidetes, and fungal phylum Ascomycota were dominant in all tissues. The relative abundance of these dominant communities showed significantly differences between Q. aliena tissues with or without H. erinaceus. Bacterial genus Pseudomonas and fungal genus Cryptosporiopsis were species-rich in Q. aliena root infected by H. erinaceus hyphae. This study demonstrated that the endophytic microbial community structure and dominant species varied in Q. aliena mycorrhized with H. erinaceus.