RESUMEN
Ubiquitination is a crucial post-translational modification of proteins that mediates the degradation or functional regulation of specific proteins. This process participates in various biological processes such as cell growth, development, and signal transduction. E3 ubiquitin ligases play both positive and negative regulatory roles in osteogenesis and differentiation by ubiquitination-mediated degradation or stabilization of transcription factors, signaling molecules, and cytoskeletal proteins. These activities affect the proliferation, differentiation, survival, and bone formation of osteoblasts (OBs). In recent years, advances in genomics, transcriptomics, and proteomics have led to a deeper understanding of the classification, function, and mechanisms of action of E3 ubiquitin ligases. This understanding provides new insights and approaches for revealing the molecular regulatory mechanisms of bone formation and identifying therapeutic targets for bone metabolic diseases. This review discusses the research progress and significance of the positive and negative regulatory roles and mechanisms of E3 ubiquitin ligases in the process of osteogenic differentiation. Additionally, the review highlights the role of E3 ubiquitin ligases in bone-related diseases. A thorough understanding of the role and mechanisms of E3 ubiquitin ligases in osteogenic differentiation could provide promising therapeutic targets for bone tissue engineering based on stem cells.
RESUMEN
Electrospun membranes are widely used in tissue engineering. Regretfully, there is limited research on how its morphological characteristics precisely regulate macrophage activation and immune response. Therefore, electrospun poly-l-lactic acid (PLLA) membranes with different alignments (align and random) and diameters (nanoscale and microscale) are prepared to investigate the effects of different surface morphologies on M2 macrophage polarization. Additionally, transcriptome, proteome, and phosphoproteome sequencings are combined to examine the underlying regulatory mechanisms. The results show that the electrospun PLLA membranes with different surface morphologies have good biocompatibility and can regulate the phenotype and function of macrophages by changing the micromorphology of the matrix surface. Especially, macrophages cultured on the electrospun membranes of the A600 group exhibit higher M2 macrophage polarization than the other three groups. Furthermore, the findings demonstrate that electrospun PLLA membranes enhance AMP-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) signaling activation by upregulating the expression of integrin phosphoenolpyruvate carboxykinase 2 (PCK2), which is critical for M2 macrophage polarization. Taken together, electrospun PLLA membranes promote M2 macrophage polarization by regulating the PCK2/AMPK/mTOR signaling pathway. This research can provide further theoretical bases for scaffold design, immunoregulatory mechanisms, and clinical application based on electrospinning technology in the future.
