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International Journal of Molecular... Jun 2017The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the... (Review)
Review
The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.
Topics: Animals; Bone Diseases; Bone and Bones; Drug Delivery Systems; Drug Discovery; Durapatite; Humans; Mesenchymal Stem Cells; Osteoblasts; Osteoclasts
PubMed: 28644392
DOI: 10.3390/ijms18071345 -
Chinese Journal of Traumatology =... Dec 2020In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections.... (Review)
Review
In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.
Topics: Anti-Bacterial Agents; Bone and Bones; Cellular Microenvironment; Humans; Immune System; Lymphocyte Subsets; Osteitis; Osteoblasts; Osteoclasts; Staphylococcal Infections
PubMed: 32847694
DOI: 10.1016/j.cjtee.2020.05.009 -
Frontiers in Immunology 2020The complex crosstalk between the immune and the skeletal systems plays an indispensable role in the maintenance of skeletal homeostasis. Various cytokines are involved,... (Review)
Review
The complex crosstalk between the immune and the skeletal systems plays an indispensable role in the maintenance of skeletal homeostasis. Various cytokines are involved, including interleukin (IL)-17A. A variety of immune and inflammatory cells produces IL-17A, especially Th17 cells, a subtype of CD4 T cells. IL-17A orchestrates diverse inflammatory and immune processes. IL-17A induces direct and indirect effects on osteoclasts. The dual role of IL-17A on osteoclasts partly depends on its concentrations and interactions with other factors. Interestingly, IL-17A exerts a dual role in osteoblasts . IL-17A is a bone-destroying cytokine in numerous immune-mediated bone diseases including postmenopausal osteoporosis (PMOP), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA). This review will summarize and discuss the pathophysiological roles of IL-17A on the skeletal system and its potential strategies for application in immune-mediated bone diseases.
Topics: Arthritis, Psoriatic; Arthritis, Rheumatoid; Cytokines; Humans; Interleukin-17; Osteoblasts; Osteoclasts; Osteoporosis, Postmenopausal; Signal Transduction; Spondylarthritis; Th17 Cells
PubMed: 33613566
DOI: 10.3389/fimmu.2020.625034 -
Nutrition (Burbank, Los Angeles County,... May 2012Dynapenia (pronounced dahy-nuh-pē-nē-a, Greek translation for poverty of strength, power, or force) is the age-associated loss of muscle strength that is not caused by... (Review)
Review
Dynapenia (pronounced dahy-nuh-pē-nē-a, Greek translation for poverty of strength, power, or force) is the age-associated loss of muscle strength that is not caused by neurologic or muscular diseases. Dynapenia predisposes older adults to an increased risk for functional limitations and mortality. For the past several decades, the literature has largely focused on muscle size as the primary cause of dynapenia; however, recent findings have clearly demonstrated that muscle size plays a relatively minor role. Conversely, subclinical deficits in the structure and function of the nervous system and/or impairments in the intrinsic force-generating properties of skeletal muscle are potential antecedents to dynapenia. This review highlights in the contributors to dynapenia and the etiology and risk factors that predispose individuals to dynapenia. In addition, we address the role of nutrition in the muscular and neurologic systems for the preservation of muscle strength throughout the life span.
Topics: Adult; Aging; Humans; Muscle Strength; Muscle Weakness; Muscle, Skeletal; Nutritional Physiological Phenomena; Risk Factors; Sarcopenia
PubMed: 22469110
DOI: 10.1016/j.nut.2011.12.002 -
Prenatal Diagnosis May 2022We conducted a systematic review and meta-analysis to determine the diagnostic yield of exome sequencing (ES) for prenatal diagnosis of fetal structural anomalies, where... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis to determine the diagnostic yield of exome sequencing (ES) for prenatal diagnosis of fetal structural anomalies, where karyotype/chromosomal microarray (CMA) is normal.
METHODS
Following electronic searches of four databases, we included studies with ≥10 structurally abnormal fetuses undergoing ES or whole genome sequencing. The incremental diagnostic yield of ES over CMA/karyotype was calculated and pooled in a meta-analysis. Sub-group analyses investigated effects of case selection and fetal phenotype on diagnostic yield.
RESULTS
We identified 72 reports from 66 studies, representing 4350 fetuses. The pooled incremental yield of ES was 31% (95% confidence interval (CI) 26%-36%, p < 0.0001). Diagnostic yield was significantly higher for cases pre-selected for likelihood of monogenic aetiology compared to unselected cases (42% vs. 15%, p < 0.0001). Diagnostic yield differed significantly between phenotypic sub-groups, ranging from 53% (95% CI 42%-63%, p < 0.0001) for isolated skeletal abnormalities, to 2% (95% CI 0%-5%, p = 0.04) for isolated increased nuchal translucency.
CONCLUSION
Prenatal ES provides a diagnosis in an additional 31% of structurally abnormal fetuses when CMA/karyotype is non-diagnostic. The expected diagnostic yield depends on the body system(s) affected and can be optimised by pre-selection of cases following multi-disciplinary review to determine that a monogenic cause is likely.
Topics: Exome; Female; Humans; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Ultrasonography, Prenatal; Exome Sequencing
PubMed: 35170059
DOI: 10.1002/pd.6115 -
Faculty Reviews 2021Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with... (Review)
Review
Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with multi-system comorbidities. Caused mainly by pathogenic variants in the (methyl CpG binding protein 2) gene, it is the second leading genetic cause of intellectual disability in girls after Down syndrome. RTT affects not only neurological function but also a wide array of non-neurological organs. RTT-related disorders involve abnormalities of the respiratory, cardiovascular, digestive, metabolic, skeletal, endocrine, muscular, and urinary systems and immune response. Here, we review the different aspects of RTT affecting the main peripheral groups of organs and sometimes occurring independently of nervous system defects.
PubMed: 34308425
DOI: 10.12703/r/10-59 -
Journal of Human Hypertension Sep 2015There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former... (Review)
Review
There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.
Topics: Aldosterone; Animals; Blood Pressure; Calcium; Cardiovascular Diseases; Humans; Parathyroid Hormone; Renin-Angiotensin System; Signal Transduction; Vitamin D; Water-Electrolyte Balance
PubMed: 25631218
DOI: 10.1038/jhh.2014.125 -
Experimental Cell Research Nov 2021Muscular dystrophies are a heterogeneous group of monogenic neuromuscular disorders which lead to progressive muscle loss and degeneration of the musculoskeletal system....
Muscular dystrophies are a heterogeneous group of monogenic neuromuscular disorders which lead to progressive muscle loss and degeneration of the musculoskeletal system. The genetic causes of muscular dystrophies are well characterized, but no effective treatments have been developed so far. The discovery and application of the CRISPR/Cas system for genome editing offers a new path for disease treatment with the potential to permanently correct genetic mutations. The post-mitotic and multinucleated features of skeletal muscle provide an ideal target for CRISPR/Cas therapeutic genome editing because correction of a subpopulation of nuclei can provide benefit to the whole myofiber. In this review, we provide an overview of the CRISPR/Cas system and its derivatives in genome editing, proposing potential CRISPR/Cas-based therapies to correct diverse muscular dystrophies, and we discuss challenges for translating CRISPR/Cas genome editing to a viable therapy for permanent correction of muscular dystrophies.
Topics: Animals; CRISPR-Cas Systems; Disease Models, Animal; Dystrophin; Gene Editing; Genetic Therapy; Humans; Muscular Dystrophy, Duchenne; Mutation
PubMed: 34571006
DOI: 10.1016/j.yexcr.2021.112844 -
International Journal of... 2008Bone remodeling is characterized by spatial and temporal coupling of bone resorption and formation and is necessary for skeletal growth and normal bone structure... (Review)
Review
Bone remodeling is characterized by spatial and temporal coupling of bone resorption and formation and is necessary for skeletal growth and normal bone structure maintenance. Imbalance of this process is related to metabolic bone disorders such as osteoporosis or rheumatoid arthritis. For this reason, bone remodeling is under the control of several local and systemic factors, including molecules of the immune system. The importance of the interplay of both the skeletal and immune systems is reflected by the emerging interdisciplinary research field, called osteoimmunology, focused on common aspects of osteology and immunology. This review focuses on the role of inflammatory mediators, such as cytokines in bone remodeling and, in particular, a subfamily of chemotactic cytokines or chemokines which are involved not only in several aspects of physiological bone remodeling but also in pathological bone disorders, such as rheumatoid arthritis or osteoporosis. Understanding the role of inflammation and chemokines will provide new insights for the treatment of diseases affecting both skeletal and immune systems, by the development of new therapeutic strategies targeting common inflammatory mediators.
Topics: Animals; Bone Remodeling; Chemokine CXCL12; Chemokines; Humans; Immune System; Inflammation Mediators; Receptor Activator of Nuclear Factor-kappa B
PubMed: 18831915
DOI: 10.1177/039463200802100301 -
Bone May 2019The musculoskeletal system includes skeletal muscles, bones and innervating axons from neurons in the central and peripheral nervous systems. Together, they form the... (Review)
Review
The musculoskeletal system includes skeletal muscles, bones and innervating axons from neurons in the central and peripheral nervous systems. Together, they form the largest structure in the body. They also initiate and coordinate locomotion, provide structural stability, and contribute to metabolism and homeostasis. Because of these functions, much effort has been devoted to ascertaining the impact of acute and chronic stress, such as disease, injury and aging, on the musculoskeletal system. This review will examine the role of the nervous system in the deleterious changes that accrue in skeletal muscles and bones during the progression of neurologic diseases and with advancing age.
Topics: Aging; Animals; Humans; Motor Neurons; Muscle, Skeletal; Musculoskeletal System; Neuromuscular Diseases; Neuromuscular Junction
PubMed: 30695738
DOI: 10.1016/j.bone.2019.01.023