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Cold Spring Harbor Perspectives in... Dec 2018Mineralized "hard" tissues of the skeleton possess unique biomechanical properties to support the body weight and movement and act as a source of essential minerals... (Review)
Review
Mineralized "hard" tissues of the skeleton possess unique biomechanical properties to support the body weight and movement and act as a source of essential minerals required for critical body functions. For a long time, extracellular matrix (ECM) mineralization in the vertebrate skeleton was considered as a passive process. However, the explosion of genetic studies during the past decades has established that this process is essentially controlled by multiple genetic pathways. These pathways regulate the homeostasis of ionic calcium and inorganic phosphate-two mineral components required for bone mineral formation, the synthesis of mineral scaffolding ECM, and the maintainence of the levels of the inhibitory organic and inorganic molecules controlling the process of mineral crystal formation and its growth. More recently, intracellular enzyme regulators of skeletal tissue mineralization have been identified. The current review will discuss the key determinants of ECM mineralization in bone and propose a unified model explaining this process.
Topics: Bone and Bones; Calcification, Physiologic; Calcium; Extracellular Matrix; Fibril-Associated Collagens; Homeostasis; Humans; Phosphates
PubMed: 29610149
DOI: 10.1101/cshperspect.a031229 -
International Journal of Nanomedicine 2016Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form... (Review)
Review
Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization-remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide.
Topics: Bone and Bones; Calcification, Physiologic; Calcium; Humans; Phosphates; Tooth; Tooth Demineralization; Tooth Remineralization
PubMed: 27695330
DOI: 10.2147/IJN.S107624 -
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 -
Journal of Cellular and Molecular... Sep 2010Arterial calcifications as found with various imaging techniques, like plain X-ray, computed tomography or ultrasound are associated with increased cardiovascular risk.... (Review)
Review
Arterial calcifications as found with various imaging techniques, like plain X-ray, computed tomography or ultrasound are associated with increased cardiovascular risk. The prevalence of arterial calcification increases with age and is stimulated by several common cardiovascular risk factors. In this review, the clinical importance of arterial calcification and the currently known proteins involved are discussed. Arterial calcification is the result of a complex interplay between stimulating (bone morphogenetic protein type 2 [BMP-2], RANKL) and inhibitory (matrix Gla protein, BMP-7, osteoprotegerin, fetuin-A, osteopontin) proteins. Vascular calcification is especially prevalent and related to adverse outcome in patients with renal insufficiency and diabetes mellitus. We address the special circumstances and mechanisms in these patient groups. Treatment and prevention of arterial calcification is possible by the use of specific drugs. However, it remains to be proven that reduction of vascular calcification in itself leads to a reduced cardiovascular risk.
Topics: Arteries; Calcinosis; Cardiovascular Diseases; Humans; Risk Factors
PubMed: 20716128
DOI: 10.1111/j.1582-4934.2010.01139.x -
Science Advances Jul 2016Calcifying marine phytoplankton-coccolithophores- are some of the most successful yet enigmatic organisms in the ocean and are at risk from global change. To better... (Review)
Review
Calcifying marine phytoplankton-coccolithophores- are some of the most successful yet enigmatic organisms in the ocean and are at risk from global change. To better understand how they will be affected, we need to know "why" coccolithophores calcify. We review coccolithophorid evolutionary history and cell biology as well as insights from recent experiments to provide a critical assessment of the costs and benefits of calcification. We conclude that calcification has high energy demands and that coccolithophores might have calcified initially to reduce grazing pressure but that additional benefits such as protection from photodamage and viral/bacterial attack further explain their high diversity and broad spectrum ecology. The cost-benefit aspect of these traits is illustrated by novel ecosystem modeling, although conclusive observations remain limited. In the future ocean, the trade-off between changing ecological and physiological costs of calcification and their benefits will ultimately decide how this important group is affected by ocean acidification and global warming.
Topics: Calcification, Physiologic; Calcium Carbonate; Ecosystem; Global Warming; Haptophyta; Hydrogen-Ion Concentration; Oceans and Seas; Photosynthesis; Seawater
PubMed: 27453937
DOI: 10.1126/sciadv.1501822 -
The New England Journal of Medicine May 1999Although ultrasound therapy is used to treat calcific tendinitis of the shoulder, its efficacy has not been rigorously evaluated. We conducted a randomized, double-blind... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND AND METHODS
Although ultrasound therapy is used to treat calcific tendinitis of the shoulder, its efficacy has not been rigorously evaluated. We conducted a randomized, double-blind comparison of ultrasonography and sham insonation in patients with symptomatic calcific tendinitis verified by radiography. Patients were assigned to receive 24 15-minute sessions of either pulsed ultrasound (frequency, 0.89 MHz; intensity, 2.5 W per square centimeter; pulsed mode, 1:4) or an indistinguishable sham treatment to the area over the calcification. The first 15 treatments were given daily (five times per week), and the remainder were given three times a week for three weeks. Randomization was conducted according to shoulders rather than patients, so a patient with bilateral tendinitis might receive either or both therapies.
RESULTS
We enrolled 63 consecutive patients (70 shoulders). Fifty-four patients (61 shoulders) completed the study. There were 32 shoulders in the ultrasound-treatment group and 29 in the sham-treatment group. After six weeks of treatment, calcium deposits had resolved in six shoulders (19 percent) in the ultrasound-treatment group and decreased by at least 50 percent in nine shoulders (28 percent), as compared with respective values of zero and three (10 percent) in the sham-treatment group (P=0.003). At the nine-month follow-up visit, calcium deposits had resolved in 13 shoulders (42 percent) in the ultrasound-treatment group and improved in 7 shoulders (23 percent), as compared with respective values of 2 (8 percent) and 3 (12 percent) in the sham-treatment group (P=0.002). At the end of treatment, patients who had received ultrasound treatment had greater decreases in pain and greater improvements in the quality of life than those who had received sham treatment; at nine months, the differences between the groups were no longer significant.
CONCLUSIONS
In patients with symptomatic calcific tendinitis of the shoulder, ultrasound treatment helps resolve calcifications and is associated with short-term clinical improvement.
Topics: Calcinosis; Double-Blind Method; Humans; Middle Aged; Pain Measurement; Quality of Life; Radiography; Range of Motion, Articular; Rotator Cuff; Shoulder; Tendinopathy; Treatment Outcome; Ultrasonic Therapy
PubMed: 10332014
DOI: 10.1056/NEJM199905203402002 -
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 -
Matrix Biology : Journal of the... 2016The skeleton is unique from all other tissues in the body because of its ability to mineralize. The incorporation of mineral into bones and teeth is essential to give... (Review)
Review
The skeleton is unique from all other tissues in the body because of its ability to mineralize. The incorporation of mineral into bones and teeth is essential to give them strength and structure for body support and function. For years, researchers have wondered how mineralized tissues form and repair. A major focus in this context has been on the role of the extracellular matrix, which harbors key regulators of the mineralization process. In this introductory minireview, we will review some key concepts of matrix biology as it related to mineralized tissues. Concurrently, we will highlight the subject of this special issue covering many aspects of mineralized tissues, including bones and teeth and their associated structures cartilage and tendon. Areas of emphasis are on the generation and analysis of new animal models with permutations of matrix components as well as the development of new approaches for tissue engineering for repair of damaged hard tissue. In assembling key topics on mineralized tissues written by leaders in our field, we hope the reader will get a broad view of the topic and all of its fascinating complexities.
Topics: Animals; Bone and Bones; Calcification, Physiologic; Extracellular Matrix; Humans; Models, Animal; Tissue Engineering; Tooth; Tooth Calcification
PubMed: 27131884
DOI: 10.1016/j.matbio.2016.04.003 -
The American Journal of Pathology May 2022Pathologic soft tissue calcification can occur in both genetic and acquired clinical conditions, causing significant morbidity and mortality. Although the... (Review)
Review
Pathologic soft tissue calcification can occur in both genetic and acquired clinical conditions, causing significant morbidity and mortality. Although the pathomechanisms of pathologic calcification are poorly understood, major progress has been made in recent years in defining the underlying genetic defects in Mendelian disorders of ectopic calcification. This review presents an overview of the pathophysiology of five monogenic disorders of pathologic calcification: pseudoxanthoma elasticum, generalized arterial calcification of infancy, arterial calcification due to deficiency of CD73, ankylosis, and progeria. These hereditary disorders, caused by mutations in genes encoding ATP binding cassette subfamily C member 6, ectonucleotide pyrophosphatase/phosphodiesterase 1, CD73, progressive ankylosis protein, and lamin A/C proteins, respectively, are inorganic pyrophosphate (PPi) deficiency syndromes with reduced circulating levels of PPi, the principal physiologic inhibitor of calcium hydroxyapatite deposition in soft connective tissues. In addition to genetic diseases, PPi deficiency has been encountered in acquired clinical conditions accompanied by pathologic calcification. Because specific and effective treatments are lacking for pathologic calcification, the unifying finding of PPi deficiency suggests that PPi-targeted therapies may be beneficial to counteract pathologic soft tissue calcification in both genetic and acquired diseases.
Topics: Ankylosis; Calcinosis; Choristoma; Diphosphates; Humans; Pseudoxanthoma Elasticum; Syndrome; Vascular Calcification
PubMed: 35182493
DOI: 10.1016/j.ajpath.2022.01.012 -
International Journal of Molecular... Apr 2021Pathological (ectopic) mineralization of soft tissues occurs during aging, in several common conditions such as diabetes, hypercholesterolemia, and renal failure and in... (Review)
Review
Pathological (ectopic) mineralization of soft tissues occurs during aging, in several common conditions such as diabetes, hypercholesterolemia, and renal failure and in certain genetic disorders. Pseudoxanthoma elasticum (PXE), a multi-organ disease affecting dermal, ocular, and cardiovascular tissues, is a model for ectopic mineralization disorders. ABCC6 dysfunction is the primary cause of PXE, but also some cases of generalized arterial calcification of infancy (GACI). ABCC6 deficiency in mice underlies an inducible dystrophic cardiac calcification phenotype (DCC). These calcification diseases are part of a spectrum of mineralization disorders that also includes Calcification of Joints and Arteries (CALJA). Since the identification of ABCC6 as the "PXE gene" and the development of several animal models (mice, rat, and zebrafish), there has been significant progress in our understanding of the molecular genetics, the clinical phenotypes, and pathogenesis of these diseases, which share similarities with more common conditions with abnormal calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi) and adenosine by the ectonucleotidases NPP1 and CD73 (NT5E). PPi is a potent endogenous inhibitor of calcification, whereas adenosine indirectly contributes to calcification inhibition by suppressing the synthesis of tissue non-specific alkaline phosphatase (TNAP). At present, therapies only exist to alleviate symptoms for both PXE and GACI; however, extensive studies have resulted in several novel approaches to treating PXE and GACI. This review seeks to summarize the role of ABCC6 in ectopic calcification in PXE and other calcification disorders, and discuss therapeutic strategies targeting various proteins in the pathway (ABCC6, NPP1, and TNAP) and direct inhibition of calcification via supplementation by various compounds.
Topics: 5'-Nucleotidase; ATP-Binding Cassette Transporters; Animals; Calcification, Physiologic; Calcinosis; Diphosphates; GPI-Linked Proteins; Humans; Joint Diseases; Mice; Multidrug Resistance-Associated Proteins; Phosphoric Diester Hydrolases; Pseudoxanthoma Elasticum; Pyrophosphatases; Rats; Vascular Calcification; Vascular Diseases
PubMed: 33925341
DOI: 10.3390/ijms22094555