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Current Molecular Biology Reports

Fatma F Mohamed, Renny T Franceschi
The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies...
December 2017: Current Molecular Biology Reports
F Runa, S Hamalian, K Meade, P Shisgal, P C Gray, J A Kelber
The tumor microenvironment (TME) has been recognized as an integral component of malignancies in breast and prostate tissues, contributing in confounding ways to tumor progression, metastasis, therapy resistance and disease recurrence. Major components of the TME are immune cells, fibroblasts, pericytes, endothelial cells, mesenchymal stroma/stem cells (MSCs), and extracellular matrix (ECM) components. Herein, we discuss the molecular and cellular heterogeneity within the TME and how this presents unique challenges and opportunities for treating breast and prostate cancers...
December 2017: Current Molecular Biology Reports
Carolyne Falank, Heather Fairfield, Michaela R Reagan
This review highlights the recent advances in our understanding of adipocyte contributions to carcinogenesis or cancer disease progression for cancers in the bone. Purpose: In this review, we aim to describe bone marrow adipose tissue and discuss the soluble adipocyte-derived cytokines (adipokines) or endocrine factors, adipocyte-derived lipids, and the actual or putative juxtacrine signaling between bone marrow adipocytes and tumor cells in the bone marrow. This relationship likely affects tumor cell initiation, proliferation, metastasis, and/or drug resistance...
December 2017: Current Molecular Biology Reports
Laura R McCabe, Narayanan Parameswaran
Purpose of review: The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3-5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. Recent findings: The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs...
September 2017: Current Molecular Biology Reports
Sujoy Bhattacharya, Rajashekhar Gangaraju, Edward Chaum
Purpose of review: Progress in stem cell research for blinding diseases over the past decade is now being applied to patients with retinal degenerative diseases and soon perhaps, glaucoma. However, the field still has much to learn about the conversion of stem cells into various retinal cell types, and the potential delivery methods that will be required to optimize the clinical efficacy of stem cells delivered into the eye. Recent findings: Recent groundbreaking human clinical trials have demonstrated both the opportunities and current limitations of stem cell transplantation for retinal diseases...
September 2017: Current Molecular Biology Reports
Naira V Margaryan, Elisabeth A Seftor, Richard E B Seftor, Mary J C Hendrix
Purpose of review: Cancer is a major public health problem worldwide. In aggressive cancers, which are heterogeneous in nature, there exists a paucity of targetable molecules that can be used to predict outcome and response to therapy in patients, especially those in the high risk category with a propensity to relapse following chemotherapy. This review addresses the challenges pertinent to treating aggressive cancer cells with inherent stem cell properties, with a special focus on triple-negative breast cancer (TNBC)...
September 2017: Current Molecular Biology Reports
Krithika S Rao, Jeffrey L Spees
PURPOSE OF REVIEW: Ischemic heart disease and stroke lead to the greatest number of deaths worldwide. Despite decreased time to intervention and improvements in the standard of care, 1 out of 5 patients that survive a myocardial infarction (MI) still face long-term chronic heart failure and a 5-year mortality rate of about 50%. Based on their multi-potency for differentiation and paracrine activity, epicardial cells and their derivatives have potential to rescue jeopardized tissue and/or promote cardiac regeneration...
September 2017: Current Molecular Biology Reports
Lance A Stechschulte, Beata Lecka-Czernik
Purpose of review: Post-translational modifications (PTMs), specifically serine phosphorylation, are essential for determination and tuning up an activity of many proteins, including those that are involved in the control of gene transcription. Transcription factors PPARγ2 and RUNX2 are essential for mesenchymal stem cell (MSC) commitment to either adipocyte or osteoblast lineage. This review is summarizing current knowledge how serine phosphorylation PTMs regulate activities of both transcription factors and MSCs lineage commitment...
June 2017: Current Molecular Biology Reports
Marta Galán-Díez, Stavroula Kousteni
Purpose of review: This review focuses on evidence highlighting the bidirectional crosstalk between the hematopoietic stem cell (HSC) and their surrounding stromal cells, with a particular emphasis on cells of the osteoblast lineage. The role and molecular functions of osteoblasts in normal hematopoiesis and in myeloid hematological malignancies is discussed. Recent findings: Cells of the osteoblast lineage have emerged as potent regulators of HSC expansion that regulate their recruitment and, depending on their stage of differentiation, their activity, proliferation and differentiation along the lymphoid, myeloid and erythroid lineages...
June 2017: Current Molecular Biology Reports
Renny T Franceschi, Chunxi Ge
PURPOSE OF THE REVIEW: This review will provide a timely assessment of MAP kinase actions in bone development and homeostasis with particular emphasis on transcriptional control of the osteoblast lineage. RECENT FINDINGS: ERK and p38 MAP kinases function as transducers of signals initiated by the extracellular matrix, mechanical loading, TGF-β, BMPs and FGF2. MAPK signals may also affect and/or interact with other important pathways such as WNT and HIPPO. ERK and p38 MAP kinase pathways phosphorylate specific osteogenic transcription factors including RUNX2, Osterix, ATF4 and DLX5...
June 2017: Current Molecular Biology Reports
Lilian I Plotkin, Rafael Pacheco-Costa, Hannah M Davis
PURPOSE OF REVIEW: To describe the current knowledge on the cross-talk between connexins and microRNAs (miRs) in bone cells. RECENT FINDINGS: Connexins play a crucial role on bone development and maintenance, and disruptions in their abundance or localization can affect how bone perceives and responds to mechanical, hormonal, and pharmacological stimuli. Connexin expression can be modified by miRs, which modulate connexin mRNA and protein levels. Recently, different manners by which miRs and connexins can interact in bone have been identified, including mechanisms that mediate miR exchange between cells in direct contact through gap junctions, or between distant cells via extracellular vesicles (EVs)...
June 2017: 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
Sam Houfflyn, Christophe Matthys, Adelheid Soubry
Purpose of Review: The prevalence of obesity has increased substantially in the current generations of Western countries, and the burden of obesity-related complications has been growing steadily. In men, obesity is not only a major risk factor for serious chronic diseases, concern is growing that the reproductive capacity, and more particularly, their offspring's health may be affected. Obesity-related impaired spermatogenesis is associated with a decrease in microscopic and molecular sperm characteristics and pregnancy success...
2017: Current Molecular Biology Reports
Emma Budd, Shona Waddell, María C de Andrés, Richard O C Oreffo
Purpose of Review: Degenerative skeletal disorders including osteoarthritis (OA) and osteoporosis (OP) are the result of attenuation of tissue regeneration and lead to painful conditions with limited treatment options. Preventative measures to limit the onset of OA and OP remain a significant unmet clinical need. MicroRNAs (miRNAs) are known to be involved in the differentiation of stem cells, and in combination with stem cell therapy could induce skeletal regeneration and potentially prevent OA and OP onset...
2017: Current Molecular Biology Reports
Zoran Culig
Purpose of Review: Compensatory mechanisms leading to increased androgen receptor expression and activity after androgen ablation or anti-androgen treatment have been identified in prostate cancer. After hydroxyflutamide and bicalutamide were used in therapy of prostate cancer over many years, novel anti-androgen enzalutamide showed improved clinical activity. However, enzalutamide resistance develops over a certain time period, and molecular mechanisms responsible for this process are heterogeneous...
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
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