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Current Molecular Biology Reports

Heather Fairfield, Clifford J Rosen, Michaela R Reagan
Sclerostin (SOST), a protein secreted from mature osteocytes in response to mechanical unloading and other stimuli, inhibits the osteogenic Wnt/β-catenin pathway in mesenchymal stem cells (MSCs) impeding their ability to differentiate into mineralizing osteoblasts. PURPOSE: This review summarizes the crosstalk between adipose tissue and bone. It also reviews the origin, regulation, and role of SOST in osteogenesis and brings attention to an emerging role of this protein in the regulation of adipogenesis...
June 2017: Current Molecular Biology Reports
Jessica Isabel Warrington, Gareth Owain Richards, Ning Wang
PURPOSE OF REVIEW: This study is to highlight recent discoveries associated with the role of calcitonin peptide family and their receptors in prostate cancer progression and bone metastasis. RECENT FINDINGS: Studies have linked adrenomedullin (AM), calcitonin (CT) and calcitonin gene-related peptide (CGRP) to the spread of prostate tumours to the bone. AM can induce a metastatic phenotype in prostate cancer cells through its action on TRPV2 calcium channels and is also capable of influencing localised levels of RANKL in the bone to favour tumourigenesis...
2017: Current Molecular Biology Reports
Jean-Etienne Bassard, Birger Lindberg Møller, Tomas Laursen
PURPOSE OF REVIEW: We provide an overview of the current knowledge on cytochrome P450-mediated metabolism organized as metabolons and factors that facilitate their stabilization. Essential parameters will be discussed including those that are commonly disregarded using the dhurrin metabolon from Sorghum bicolor as a case study. RECENT FINDINGS: Sessile plants control their metabolism to prioritize their resources between growth and development, or defense. This requires fine-tuned complex dynamic regulation of the metabolic networks involved...
2017: Current Molecular Biology Reports
Hilal Maradit Kremers, Eric A Lewallen, Andre J van Wijnen, David G Lewallen
Total hip and knee arthroplasty are effective interventions for management of end-stage arthritis. Indeed, about 7 million Americans are currently living with artificial hip and knee joints. The majority of these individuals, however, will outlive their implants and require revision surgeries, mostly due to poor implant osseointegration and aseptic loosening. Revisions are potentially avoidable with better management of patient-related risk factors that affect the osseointegration of orthopedic implants. In this review, we summarize the published clinical literature on the role of demographics, biologic factors, comorbidities, medications and aseptic loosening risk...
September 2016: Current Molecular Biology Reports
Gunes Uzer, Clinton T Rubin, Janet Rubin
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...
March 2016: Current Molecular Biology Reports
Florante Ricarte, Teruyo Nakatani, Nicola Partridge
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...
March 2016: Current Molecular Biology Reports
Erica L Clinkenbeard, Kenneth E White
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...
March 1, 2016: Current Molecular Biology Reports
Niraj Lodhi, Yingbiao Ji, Alexei Tulin
Restoring chromatin structure with high fidelity after mitosis is critical for cell survival. Transcriptional reactivation of genes is the first step toward establishing identity of the daughter cell. During mitosis, chromatin bookmarking factors associated with specific chromatin regions ensure the restoration of the original gene expression pattern in daughter cells. Recent findings have provided new insights into the mechanisms, regulation, and biological significance of gene bookmarking in eukaryotes. In this review, we discuss how epigenetic factors, such as Poly(ADP-ribose) Polymerase-1, establish epigenetic memory in mitotic chromatin...
March 2016: Current Molecular Biology Reports
Jonathan Christopher Dubé, Xue Qing David Wang, Josée Dostie
The role of genome architecture in transcription regulation has become the focus of an increasing number of studies over the past decade. Chromatin organization can have a significant impact on gene expression by promoting or restricting the physical proximity between regulatory DNA elements. Given that any change in chromatin state has the potential to alter DNA folding and the proximity between control elements, the spatial organization of chromatin is inherently linked to its molecular composition. In this review, we explore how modulators of chromatin state and organization might keep gene expression in check...
March 2016: Current Molecular Biology Reports
Christoph Rücker, Holger Kirch, Oliver Pullig, Heike Walles
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...
2016: Current Molecular Biology Reports
S Karkampouna, M Kreulen, M C Obdeijn, P Kloen, A L Dorjée, F Rivellese, A Chojnowski, I Clark, Marianna Kruithof-de Julio
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...
2016: Current Molecular Biology Reports
Jess Morhayim, Resti Rudjito, Johannes P van Leeuwen, Marjolein van Driel
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...
2016: Current Molecular Biology Reports
Jesus Delgado-Calle, Teresita Bellido
For many years, osteocytes have been the forgotten bone cells and considered as inactive spectators buried in the bone matrix. We now know that osteocytes detect and respond to mechanical and hormonal stimuli to coordinate bone resorption and bone formation. Osteocytes are currently considered a major source of molecules that regulate the activity of osteoclasts and osteoblasts, such as RANKL and sclerostin; and genetic and pharmacological manipulations of either molecule markedly affect bone homeostasis. Besides playing a role in physiological bone homeostasis, accumulating evidence supports the notion that dysregulation of osteocyte function and alteration of osteocyte life-span underlies the pathophysiology of skeletal disorders characterized by loss bone mass and increased bone fragility, as well as the damaging effects of cancer in bone...
December 2015: Current Molecular Biology Reports
Helen P Makarenkova, Darlene A Dartt
Lacrimal gland (LG) is an exocrine tubuloacinar gland that secretes the aqueous layer of the tear film. LG epithelium is composed of ductal, acinar, and myoepithelial cells (MECs) bordering the basal lamina and separating the epithelial layer from the extracellular matrix. Mature MECs have contractile ability and morphologically resemble smooth muscle cells; however, they exhibit features typical for epithelial cells, such as the presence of specific cytokeratin filaments. Increasing evidence supports the assertion that myoepithelial cells (MECs) play key roles in the lacrimal gland development, homeostasis, and stabilizing the normal structure and polarity of LG secretory acini...
September 1, 2015: Current Molecular Biology Reports
Ryan Berry, Matthew S Rodeheffer, Clifford J Rosen, Mark C Horowitz
The formation of brown, white and beige adipocytes have been a subject of intense scientific interest in recent years due to the growing obesity epidemic in the United States and around the world. This interest has led to the identification and characterization of specific tissue resident progenitor cells that give rise to each adipocyte population in vivo. However, much still remains to be discovered about each progenitor population in terms of their "niche" within each tissue and how they are regulated at the cellular and molecular level during healthy and diseased states...
September 2015: Current Molecular Biology Reports
Noriaki Ono, Henry M Kronenberg
Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment...
September 2015: Current Molecular Biology Reports
Jennifer Robinson, Alina O'Brien, Jing Chen, Sunil Wadhwa
The secondary cartilage of the mandibular condyle is unique as it undergoes endochondral ossification during growth and robustly remodels in response to changes in its mechanical loading environment. This cartilage is derived from mesenchymal progenitor cells that express markers of early osteoblast differentiation, namely alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2). Interestingly, these progenitor cells then differentiate into cartilage with appropriate mechanical loading. Our laboratory has determined that these cells can be labeled by osteoblast progenitor cell markers, including the 3...
September 2015: Current Molecular Biology Reports
Nathaniel A Dyment, Jenna L Galloway
Understanding the molecular and cellular mechanisms underlying tissue turnover and repair are essential towards addressing pathologies in aging, injury and disease. Each tissue has distinct means of maintaining homeostasis and healing after injury. For some, resident stem cell populations mediate both of these processes. These stem cells, by definition, are self renewing and give rise to all the differentiated cells of that tissue. However, not all organs fit with this traditional stem cell model of regeneration, and some do not appear to harbor somatic stem or progenitor cells capable of multilineage in vivo reconstitution...
September 2015: Current Molecular Biology Reports
Lorena Aguilar-Arnal, Paolo Sassone-Corsi
The molecular circadian clock orchestrates the daily cyclical expression of thousands of genes. Disruption of this transcriptional program leads to a variety of pathologies, including insomnia, depression and metabolic disorders. Circadian rhythms in gene expression rely on specific chromatin transitions which are ultimately coordinated by the molecular clock. As a consequence, a highly plastic and dynamic circadian epigenome can be delineated across different tissues and cell types. Intriguingly, genome topology appears to coordinate cyclic transcription at circadian interactomes, in which circadian genes are in physical contact within the cell nucleus in a time-specific manner...
March 2015: Current Molecular Biology Reports
Yung-Chia Ariel Chen, Alexei A Aravin
Transcriptional gene silencing guided by small RNAs is a process conserved from protozoa to mammals. Small RNAs loaded into Argonaute family proteins direct repressive histone modifications or DNA cytosine methylation to homologous regions of the genome. Small RNA-mediated transcriptional silencing is required for many biological processes, including repression of transposable elements, maintaining the genome stability/integrity, and epigenetic inheritance of gene expression. Here we will summarize the current knowledge about small RNA biogenesis and mechanisms of transcriptional regulation in plants, Drosophila, C...
March 1, 2015: Current Molecular Biology Reports
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