Current molecular biology reports最新文献

As our understanding of the mechanisms that govern bone development advance, the role of epigenetic modifications in these processes become increasingly evident. Interestingly, in parathyroid hormone (PTH)-induced bone metabolism and remodeling, recent evidence shows that PTH signaling employs a particular facet of the epigenetic machinery to elicit its desired effects. In this review, we briefly discuss the known epigenetic events occurring in cells of the osteoblast lineage. More specifically, we elaborate on current findings that reveal the utilization of histone deacetylating enzymes (HDACs) in PTH-regulated modulation of gene expression in bone.

The regulation of phosphate metabolism as an influence on bone homeostasis is profound. Recent advances in understanding the systemic control of Fibroblast growth factor-23 (FGF23) has uncovered novel effectors of endocrine feedback loops for calcium, phosphate, and vitamin D balance that interact with 'traditional' feedback loops for mineral metabolism. Not only are these findings re-shaping research studying phosphate handling and skeletal interactions, they have provided new therapeutic interventions. Emerging data support that the control of FGF23 production in bone and its circulating concentrations is a multi-layered process, with some influences affecting FGF23 transcription and some post-translational modification of the secreted, bioactive protein. Additionally, the actions of FGF23 on its target tissues via its co-receptor αKlotho, are subject to regulatory events just coming to light. The recent findings of systemic influences on circulating FGF23 and the downstream manifestations on bone homeostasis will be reviewed herein.

Mechanoresponses in mesenchymal stem cells (MSCs) guide both differentiation and function. In this review, we focus on advances in0 our understanding of how the cytoplasmic cytoskeleton, nuclear envelope and nucleoskeleton, which are connected via LINC (Linker of Nucleoskeleton and Cytoskeleton) complexes, are emerging as an integrated dynamic signaling platform to regulate MSC mechanobiology. This dynamic interconnectivity affects mechanical signaling and transfer of signals into the nucleus. In this way, nuclear and LINC-mediated cytoskeletal connectivity play a critical role in maintaining mechanical signaling that affects MSC fate by serving as both mechanosensory and mechanoresponsive structures. We review disease and age related compromises of LINC complexes and nucleoskeleton that contribute to the etiology of musculoskeletal diseases. Finally we invite the idea that acquired dysfunctions of LINC might be a contributing factor to conditions such as aging, microgravity and osteoporosis and discuss potential mechanical strategies to modulate LINC connectivity to combat these conditions.

Dupuytren's disease is a connective tissue disorder of the hand causing excessive palmar fascial fibrosis with associated finger contracture and disability. The aetiology of the disease is heterogeneous, with both genetic and environmental components. The connective tissue is abnormally infiltrated by myofibroblasts that deposit collagen and other extracellular matrix proteins. We describe the clinical profile of Dupuytren's disease along with current therapeutic schemes. Recent findings on molecular and cellular parameters that are dysregulated in Dupuytren's disease, which may contribute to the onset of the disease, and the role of resident inflammation promoting fibrosis, are highlighted. We review recent literature focusing on non-myofibroblast cell types (stem cell-like cells), their pro-inflammatory and pro-fibrotic role that may account for abnormal wound healing response.

Extracellular vesicles (EVs), spherical bilayered proteolipids, behave as paracrine effectors since they are released from cells to deliver signals to other cells. They control a diverse range of biological processes by transferring proteins, lipids, and nucleic acids between cells and are secreted by a wide spectrum of cell types and are found in various biological fluids. EVs are formed at the plasma membrane or in endosomes and are heterogeneous in size and composition. Increasing understanding of the working mechanisms is promising for therapeutic and diagnostic opportunities. In this review, we will focus on the recent developments in this emerging field with special emphasis on the role of EVs in the bone microenvironment, with a central role for the osteoblasts in the communication with a diversity of cells, including bone metastases.

Despite the great regenerative potential of human bone, large bone defects are a serious condition. Commonly, large defects are caused by trauma, bone disease, malignant tumor removal, and infection or medication-related osteonecrosis. Large defects necessitate clinical treatment in the form of autologous bone transplantation or implantation of biomaterials as well as the application of other available methods that enhance bone defect repair. The development and application of prevascularized bone implants are closely related to the development animal models and require dedicated methods in order to reliably predict possible clinical outcomes and the efficacy of implants. Cell sheet engineering, 3D-printing, arteriovenous loops, and naturally derived decellularized scaffolds and their respective testings in animal models are presented as alternative to the autologous bone graft in this article.