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Nutrients Sep 2020Over 200 million people suffer from osteoporosis worldwide. Individuals with osteoporosis have increased rates of bone resorption while simultaneously having impaired... (Review)
Review
Over 200 million people suffer from osteoporosis worldwide. Individuals with osteoporosis have increased rates of bone resorption while simultaneously having impaired osteogenesis. Most current treatments for osteoporosis focus on anti-resorptive methods to prevent further bone loss. However, it is important to identify safe and cost-efficient treatments that not only inhibit bone resorption, but also stimulate anabolic mechanisms to upregulate osteogenesis. Recent data suggest that macrophage polarization may contribute to osteoblast differentiation and increased osteogenesis as well as bone mineralization. Macrophages exist in two major polarization states, classically activated macrophages (M1) and alternatively activated macrophage (M2) macrophages. The polarization state of macrophages is dependent on molecules in the microenvironment including several cytokines and chemokines. Mechanistically, M2 macrophages secrete osteogenic factors that stimulate the differentiation and activation of pre-osteoblastic cells, such as mesenchymal stem cells (MSC's), and subsequently increase bone mineralization. In this review, we cover the mechanisms by which M2 macrophages contribute to osteogenesis and postulate the hypothesis that regulating macrophage polarization states may be a potential treatment for the treatment of osteoporosis.
Topics: Animals; Bone Morphogenetic Protein 2; Calcification, Physiologic; Cell Differentiation; Cell Polarity; Humans; Interleukin-4; Macrophage Activation; Macrophages; Osteoblasts; Osteogenesis; Osteoporosis; Tumor Necrosis Factor-alpha
PubMed: 33007863
DOI: 10.3390/nu12102999 -
Journal of Radiology Case Reports Aug 2019Intracranial calcifications are frequently encountered in non-contrast computed tomography scan in both adult and pediatric age groups. They refer to calcifications... (Review)
Review
Intracranial calcifications are frequently encountered in non-contrast computed tomography scan in both adult and pediatric age groups. They refer to calcifications within the brain parenchyma or vasculature and can be classified into several major categories: physiologic/age-related, dystrophic, congenital disorders/phakomatoses, infectious, vascular, neoplastic, metabolic/endocrine, inflammatory and toxic diseases. In this updated review, we present a wide spectrum of intracranial calcifications from both pediatric and adult populations focusing on their pattern, size and location.
Topics: Brain; Brain Diseases; Calcification, Physiologic; Calcinosis; Humans; Terminology as Topic; Tomography, X-Ray Computed
PubMed: 31558966
DOI: 10.3941/jrcr.v13i8.3633 -
Nature Communications Oct 2022Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for...
Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for collagen maturation. Here, we demonstrate that Vitamin C epigenetically orchestrates osteogenic differentiation and function by modulating chromatin accessibility and priming transcriptional activity. Vitamin C regulates histone demethylation (H3K9me3 and H3K27me3) and promotes TET-mediated 5hmC DNA hydroxymethylation at promoters, enhancers and super-enhancers near bone-specific genes. This epigenetic circuit licenses osteoblastogenesis by permitting the expression of all major pro-osteogenic genes. Osteogenic cell differentiation is strictly and continuously dependent on Vitamin C, whereas Vitamin C is dispensable for adipogenesis. Importantly, deletion of 5hmC-writers, Tet1 and Tet2, in Vitamin C-sufficient murine bone causes severe skeletal defects which mimic bone phenotypes of Vitamin C-insufficient Gulo knockout mice, a model of Vitamin C deficiency and scurvy. Thus, Vitamin C's epigenetic functions are central to osteoblastogenesis and bone formation and may be leveraged to prevent common bone-degenerating conditions.
Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcification, Physiologic; Cell Differentiation; Chromatin; DNA; DNA Methylation; Histones; Mice; Osteogenesis
PubMed: 36202795
DOI: 10.1038/s41467-022-32915-8 -
IUBMB Life Jan 2022Phosphate, an essential nutrient, is available in organic and inorganic forms. The balance of phosphate is central for cellular homeostasis through the genomic roles of...
Phosphate, an essential nutrient, is available in organic and inorganic forms. The balance of phosphate is central for cellular homeostasis through the genomic roles of DNA and RNA synthesis and cell signaling processes. Therefore, an imbalance of this nutrient, manifested, either as a deficiency or excess in phosphate levels, can result in pathology, ranging from cytotoxicity to musculoskeletal defects. Inorganic phosphate (Pi) overdosing can result in a wide spectrum of cytotoxicity processes, as noted in both animal models and human studies. These include rewired cell signaling pathways, impaired bone mineralization, infertility, premature aging, vascular calcification, and renal dysfunction. This article briefly reviews the regulation of phosphate homeostasis and elaborates on cytotoxic effects of excessive Pi, as documented in cell-based models.
Topics: Animals; Calcification, Physiologic; Homeostasis; Phosphates
PubMed: 34676972
DOI: 10.1002/iub.2561 -
Nature Communications Jun 2022Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At...
Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At the end of adolescence, type H vessels differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus limit adolescent bone growth have remained ill defined. Here we show that mechanical forces, associated with increased body weight at the end of adolescence, trigger the mechanoreceptor PIEZO1 and thereby mediate enhanced production of the kinase FAM20C in osteoblasts. FAM20C, the major kinase of the secreted phosphoproteome, phosphorylates dentin matrix protein 1, previously identified as a key factor in bone mineralization. Thereupon, dentin matrix protein 1 is secreted from osteoblasts in a burst-like manner. Extracellular dentin matrix protein 1 inhibits vascular endothelial growth factor signalling by preventing phosphorylation of vascular endothelial growth factor receptor 2. Hence, secreted dentin matrix protein 1 transforms type H vessels into type L to limit bone growth activity and enhance bone mineralization. The discovered mechanism may suggest new options for the treatment of diseases characterised by aberrant activity of bone and vessels such as osteoarthritis, osteoporosis and osteosarcoma.
Topics: Adolescent; Bone Development; Bone Matrix; Calcification, Physiologic; Extracellular Matrix Proteins; Humans; Ion Channels; Morphogenesis; Neovascularization, Physiologic; Phosphoproteins; Stress, Mechanical; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
PubMed: 35650194
DOI: 10.1038/s41467-022-30618-8 -
Nutrients Oct 2021The accretion of adequate mineral content is essential for normal bone mineralization [...].
The accretion of adequate mineral content is essential for normal bone mineralization [...].
Topics: Calcification, Physiologic; Calcium; Humans; Infant, Newborn; Infant, Premature; Phosphorus
PubMed: 34835948
DOI: 10.3390/nu13113692 -
Orphanet Journal of Rare Diseases Aug 2023Osteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and... (Review)
Review
Osteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and complex pathogenic mechanisms. The previous classifications lack structure and scientific basis and have poor applicability. In this paper, we summarize and sort out the pathogenic mechanisms of OI, and analyze the molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects(synthesis defects, processing defects, post-translational modification defects, folding and cross-linking defects), bone mineralization disorders, osteoblast differentiation and functional defects respectively, and also generalize several new untyped OI-causing genes and their pathogenic mechanisms, intending to provide the evidence of classification and a scientific basis for the precise diagnosis and treatment of OI.
Topics: Humans; Osteogenesis Imperfecta; Collagen Type I; Osteogenesis; Calcification, Physiologic; Bone Diseases; Mutation
PubMed: 37559063
DOI: 10.1186/s13023-023-02849-5 -
International Journal of Molecular... Oct 2020In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in... (Review)
Review
In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in benign lesions and in other subtypes of thyroid carcinomas. Thyroid calcifications are classified according to their diameter and location. At ultrasonography, microcalcifications appear as hyperechoic spots ≤ 1 mm in diameter and can be named as stromal calcification, bone formation, or psammoma bodies (PBs), whereas calcifications > 1 mm are macrocalcifications. The mechanism of their formation is still poorly understood. Microcalcifications are generally accepted as a reliable indicator of malignancy as they mostly represent PBs. In order to progress in terms of the understanding of the mechanisms behind calcification occurring in thyroid tumors in general, and in PTC in particular, we decided to use histopathology as the basis of the possible cellular and molecular mechanisms of calcification formation in thyroid cancer. We explored the involvement of molecules such as runt-related transcription factor-2 (Runx-2), osteonectin/secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteopontin (OPN) in the formation of calcification. The present review offers a novel insight into the mechanisms underlying the development of calcification in thyroid cancer.
Topics: Animals; Calcification, Physiologic; Calcinosis; Humans; Models, Biological; Osteopontin; Thyroid Gland; Thyroid Neoplasms
PubMed: 33086487
DOI: 10.3390/ijms21207718 -
CMAJ : Canadian Medical Association... Aug 2021
Topics: Aged; Calcification, Physiologic; Dyspnea; Fatigue; Humans; Male; Pericarditis, Constrictive; Tomography, X-Ray Computed; Weight Loss
PubMed: 34426455
DOI: 10.1503/cmaj.202346-f -
Molecules (Basel, Switzerland) Feb 2020Biomimetic molecular design is a promising approach for generating functional biomaterials such as cell membrane mimetic blood-compatible surfaces, mussel-inspired... (Review)
Review
Biomimetic molecular design is a promising approach for generating functional biomaterials such as cell membrane mimetic blood-compatible surfaces, mussel-inspired bioadhesives, and calcium phosphate cements for bone regeneration. Polyphosphoesters (PPEs) are candidate biomimetic polymer biomaterials that are of interest due to their biocompatibility, biodegradability, and structural similarity to nucleic acids. While studies on the synthesis of PPEs began in the 1970s, the scope of their use as biomaterials has increased in the last 20 years. One advantageous property of PPEs is their molecular diversity due to the presence of multivalent phosphorus in their backbones, which allows their physicochemical and biointerfacial properties to be easily controlled to produce the desired molecular platforms for functional biomaterials. Polyphosphodiesters (PPDEs) are analogs of PPEs that have recently attracted interest due to their strong affinity for biominerals. This review describes the fundamental properties of PPDEs and recent research in the field of macromolecular bone therapeutics.
Topics: Animals; Biocompatible Materials; Biomimetic Materials; Bone Regeneration; Calcification, Physiologic; Cell Differentiation; Esters; Humans; Materials Testing; Nanoparticles; Organophosphates; Osteoblasts
PubMed: 32050545
DOI: 10.3390/molecules25030758