Current Molecular Biology Reports

Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men in the United States. In Virginia, which is a representative, ethnically diverse state of more than 8 million people that was established nearly 400 years ago, prostate cancer has the highest rate of new detection for any type of cancer. All men are at risk of developing prostate cancer regardless of demographics, but some men have an increased mortality risk due to cancer metastasis. Notably, one in five African American men will be diagnosed with prostate cancer in their lifetime and they have the highest prostate cancer mortality rate of any ethnic group in the United States, including Virginia...

Cellular senescence (CS) is increasingly implicated in the etiology of age-related diseases. While CS can facilitate physiological processes such as tissue repair and wound healing, senescent cells also contribute to pathophysiological processes involving macromolecular damage and metabolic dysregulation that characterize multiple morbid and prevalent diseases, including Alzheimer's disease, osteoarthritis, atherosclerotic vascular disease, diabetes mellitus, and idiopathic pulmonary fibrosis (IPF). Preclinical studies targeting senescent cells and the senescence-associated secretory phenotype (SASP) with "senotherapeutics" have demonstrated improvement in age-related morbidity associated with these disease states...

Purpose of review: Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic application in tissue engineering and regenerative medicine. Despite their promise, recent findings suggest that MSC replication during repair process may lead to replicative senescence and stem cell exhaustion. Here, we review the basic mechanisms of MSC senescence, how it leads to degenerative diseases, and potential treatments for such diseases. Recent findings: Emerging evidence has shown a link between senescent MSCs and degenerative diseases, especially age-related diseases such as osteoarthritis and idiopathic pulmonary fibrosis...

No abstract text is available yet for this article.

Purpose of Review: Serum phosphorus is maintained in a narrow range by balancing dietary phosphate absorption, influx and efflux of phosphorus from bone and intracellular stores, and renal reabsorption of filtered phosphate. Acute hypophosphatemia, typically caused by transient increases in cellular uptake, can lead to severe complications such as cardiopulmonary dysfunction and rhabdomyolysis that can warrant parenteral phosphate repletion. Chronic hypophosphatemia, however, generally represents true phosphate deficiency and may result in long-term metabolic and skeletal complications, particularly in children due to the critical importance of phosphorus to skeletal mineralization and longitudinal growth...

Purpose of Review-: Precise and temporal expression of Runx2 and its regulatory transcriptional network is a key determinant for the intricate cellular and developmental processes in adult bone tissue formation. This review analyzes how microRNA functions to regulate this network, and how dysregulation results in bone disorders. Recent Findings-: Similar to other biologic processes, microRNA (miRNA/miR) regulation is undeniably indispensable to bone synthesis and maintenance...

Purpose of review: Fibroblast growth factor-23 (FGF23) is the key hormone produced in bone critical for phosphate homeostasis. Elevated serum phosphorus and 1,25dihydroxyvitaminD stimulates FGF23 production to promote renal phosphate excretion and decrease 1,25dihydroxyvitaminD synthesis. Thus completing the feedback loop and suppressing FGF23. Unexpectedly, studies of common and rare heritable disorders of phosphate handling identified links between iron and FGF23 demonstrating novel regulation outside the phosphate pathway...

Purpose of Review: The phosphaturic hormone FGF23 is produced primarily in osteoblasts/osteocytes and is known to respond to increases in serum phosphate and 1,25(OH)2 vitamin D (1,25D). Novel regulators of FGF23 were recently identified, and may help explain the pathophysiologies of several diseases. This review will focus on recent studies examining the synthesis and actions of FGF23. Recent Findings: The synthesis of FGF23 in response to 1,25D is similar to other steroid hormone targets, but the cellular responses to phosphate remain largely unknown...

Purpose of review: Our goal is to comprehensively review the most recent reports of microRNA (miRNA) regulation of osteoclastogenesis. We highlight validated miRNA-target interactions and their place in the signaling networks controlling osteoclast differentiation and function. Recent findings: Using unbiased approaches to identify miRNAs of interest and reporter-3'UTR assays to validate interactions, recent studies have elucidated the impact of specific miRNA-mRNA interactions during in vitro osteoclastogenesis...

a Purpose of Review: The intervertebral discs (IVD) are an essential component of the spine. Degeneration of the discs, commonly due to age or injury, is a leading cause of chronic lower back pain. Despite its high prevalence, there is no effective treatment for disc disease due to limited understanding of disc at the cellular and molecular level. b Recent Findings: Recent research has demonstrated the importance of the intracellular developmental pathway sonic hedgehog (Shh) during the formation and postnatal maintenance of the IVD...

Purpose of review: The endplates form the interface between the rigid vertebral bodies and compliant intervertebral discs. Proper endplate function involves a balance between conflicting biomechanical and nutritional demands. This review summarizes recent data that highlight the importance of proper endplate function and the relationships between endplate dysfunction, adjacent disc degeneration, and axial low back pain. Recent findings: Changes to endplate morphology and composition that impair its permeability associate with disc degeneration...

Purpose: Age is a major risk factor for multiple disease pathologies, including chronic back pain, which stems from age-related degenerative changes to intervertebral disc tissue. Growing evidence suggest that the change in phenotype of disc cells to a senescent phenotype may be one of the major driving forces of age-associated disc degeneration. This review discusses the known stressors that promote development of senescence in disc tissue and the underlying molecular mechanisms disc cells adopt to enable their transition to a senescent phenotype...

Purpose of review: Intervertebral discs (IVD) are derived from embryonic notochord and sclerotome. The nucleus pulposus is derived from notochord while other connective tissues of the spine are derived from sclerotome. This manuscript will review the past 5 years of research into IVD development. Recent findings: Over the past several years, advances in understanding the step-wise process that govern development of the nucleus pulposus and the annulus fibrosus have been made...

Purpose of Review: Bone marrow adipocytes (BMAs) have distinct molecular properties and physiologic responses depending on their location within the skeleton. Recent Findings: This concept was introduced in the 1970s and validated more recently in the contexts of cold exposure, sympathetic tone, hematopoiesis, diabetes, lactation, fasting and caloric restriction. Summary: In this brief review, we discuss the concept of regulated vs constitutive BMAs, explore their evolutionary and microenvironmental origins, define the site-specific molecular features of BMAs, and discuss the translational implications of the dual bone marrow adipose tissue hypothesis...

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Purpose of Review: This review aims to highlight recent advances in understanding the genetic basis of intervertebral disc degeneration (IDD). Recent Findings: It has been known for some time that IDD is highly heritable. Recent studies, and in particular the availability of agnostic techniques such as genome-wide association studies, have identified new variants in a variety of genes which contribute to the risk of IDD and to back pain. Summary: A variety of genetic variants are involved in IDD...

Purpose of Review: An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Recent Findings: Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency...

Purpose of Review: The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT...

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...