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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 -
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 -
Frontiers in Bioscience (Landmark... Jan 2012This review attempts to summarize the findings made available by the literature on the mineralization of bone. The types of bone, their structures and compositions, the... (Review)
Review
This review attempts to summarize the findings made available by the literature on the mineralization of bone. The types of bone, their structures and compositions, the nature and organization of organic and inorganic matter, the organic-inorganic relationships, and the mineralization mechanism itself, are the main topics of the present review. As in other hard tissues, bone mineralization occurs in, and is conditioned by, the components of the organic matrix. Collagen fibrils have long been considered the factor that is able to induce the deposition of apatite crystallites through a process of heterogeneous nucleation. Interfibrillar non-collagenous proteins are now considered to be co-factors that permit crystallite deposition. The main components of these proteins are reviewed. It is hypothesized that two independent types of mineral are present in bone, one contained in the collagen fibrils and corresponding to the granular, electron-dense bands, and the other contained in the interfibrillar spaces and corresponding to needle- and filament-like crystals. The deposition mechanism of these mineral structures remains elusive. The formation of the crystallites through an epitaxial mechanism is discussed.
Topics: Animals; Bone Density; Bone and Bones; Calcification, Physiologic; Collagen; Glycoproteins; Humans; Lipid Metabolism; Models, Biological; Osteocalcin; Proteoglycans
PubMed: 22201735
DOI: 10.2741/3918 -
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 -
Bone Dec 2020Three physiologically mineralizing tissues - teeth, cartilage and bone - have critical common elements and important evolutionary relationships. Phylogenetically the... (Review)
Review
Three physiologically mineralizing tissues - teeth, cartilage and bone - have critical common elements and important evolutionary relationships. Phylogenetically the most ancient densely mineralized tissue is teeth. In jawless fishes without skeletons, tooth formation included epithelial transport of phosphates, a process echoed later in bone physiology. Cartilage and mineralized cartilage are skeletal elements separate from bone, but with metabolic features common to bone. Cartilage mineralization is coordinated with high expression of tissue nonspecific alkaline phosphatase and PHOSPHO1 to harvest available phosphate esters and support mineralization of collagen secreted locally. Mineralization in true bone results from stochastic nucleation of hydroxyapatite crystals within the cross-linked collagen fibrils. Mineral accumulation in dense collagen is, at least in major part, mediated by amorphous aggregates - often called Posner clusters - of calcium and phosphate that are small enough to diffuse into collagen fibrils. Mineral accumulation in membrane vesicles is widely suggested, but does not correlate with a definitive stage of mineralization. Conversely mineral deposition at non-physiologic sites where calcium and phosphate are adequate has been shown to be regulated in large part by pyrophosphate. All of these elements are present in vertebrate bone metabolism. A key biological element of bone formation is an epithelial-like cellular organization which allows control of phosphate, calcium and pH during mineralization.
Topics: Bone and Bones; Calcification, Physiologic; Minerals; Osteogenesis; Phylogeny
PubMed: 32858255
DOI: 10.1016/j.bone.2020.115621 -
Global Change Biology Jan 2020Hard, or stony, corals make rocks that can, on geological time scales, lead to the formation of massive reefs in shallow tropical and subtropical seas. In both... (Review)
Review
Hard, or stony, corals make rocks that can, on geological time scales, lead to the formation of massive reefs in shallow tropical and subtropical seas. In both historical and contemporary oceans, reef-building corals retain information about the marine environment in their skeletons, which is an organic-inorganic composite material. The elemental and isotopic composition of their skeletons is frequently used to reconstruct the environmental history of Earth's oceans over time, including temperature, pH, and salinity. Interpretation of this information requires knowledge of how the organisms formed their skeletons. The basic mechanism of formation of calcium carbonate skeleton in stony corals has been studied for decades. While some researchers consider coral skeletons as mainly passive recorders of ocean conditions, it has become increasingly clear that biological processes play key roles in the biomineralization mechanism. Understanding the role of the animal in living stony coral biomineralization and how it evolved has profound implications for interpreting environmental signatures in fossil corals to understand past ocean conditions. Here we review historical hypotheses and discuss the present understanding of how corals evolved and how their skeletons changed over geological time. We specifically explain how biological processes, particularly those occurring at the subcellular level, critically control the formation of calcium carbonate structures. We examine the different models that address the current debate including the tissue-skeleton interface, skeletal organic matrix, and biomineralization pathways. Finally, we consider how understanding the biological control of coral biomineralization is critical to informing future models of coral vulnerability to inevitable global change, particularly increasing ocean acidification.
Topics: Animals; Anthozoa; Calcification, Physiologic; Calcium Carbonate; Coral Reefs; Hydrogen-Ion Concentration; Oceans and Seas; Seawater
PubMed: 31696576
DOI: 10.1111/gcb.14912 -
International Journal of Molecular... Sep 2022Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by... (Review)
Review
Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO) flow into the vesicles via membrane transporters and enzymes located on the vesicles' membranes, while calcium ions (Ca), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca and PO in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle's membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca and PO through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes.
Topics: Bone Matrix; Calcification, Physiologic; Collagen; Extracellular Matrix; Osteoblasts; Osteocytes
PubMed: 36077336
DOI: 10.3390/ijms23179941 -
PloS One 2013Crustacean calcium bodies are epithelial sacs which contain a mineralized matrix. The objectives of this study were to describe the microscopic anatomy of calcium bodies...
Crustacean calcium bodies are epithelial sacs which contain a mineralized matrix. The objectives of this study were to describe the microscopic anatomy of calcium bodies in the terrestrial isopod Hyloniscus riparius and to establish whether they undergo molt-related structural changes. We performed 3D reconstruction of the calcium bodies from paraffin sections and analyzed their structure with light and electron microscopy. In addition, we analyzed the chemical composition of their mineralized matrices with micro-Raman spectroscopy. Two pairs of these organs are present in H. riparius. One pair is filled with bacteria while the other pair is not. In non-molting animals, the bacteria-filled calcium bodies contain apatite crystals and the bacteria-free calcium bodies enclose CaCO3-containing concretions with little organic matrix. During preparation for molt, an additional matrix layer is deposited in both pairs of calcium bodies. In the bacteria-filled calcium bodies it contains a mixture of calcium carbonate and calcium phosphate, whereas only calcium carbonate is present in bacteria-free calcium bodies. After ecdysis, all mineral components in bacteria-free calcium bodies and the additional matrix layer in bacteria-filled calcium bodies are completely resorbed. During calcium resorption, the apical surface of the calcium body epithelium is deeply folded and electron dense granules are present in spaces between epithelial cells. Our results indicate that the presence of bacteria might be linked to calcium phosphate mineralization. Calcium bodies likely provide a source of calcium and potentially phosphate for the mineralization of the new cuticle after molt. Unlike other terrestrial isopods, H. riparius does not form sternal CaCO3 deposits and the bacteria-free calcium bodies might functionally replace them in this species.
Topics: Animals; Bacteria; Calcification, Physiologic; Calcium; Calcium Carbonate; Epithelium; Isopoda; Minerals; Molting; Spectrum Analysis, Raman
PubMed: 23554963
DOI: 10.1371/journal.pone.0058968 -
JCI Insight Dec 2023Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23...
Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23 excess, impaired skeletal growth, and osteomalacia. Blocking FGF23 became an effective therapeutic strategy in X-linked hypophosphatemia, but testing remains limited in autosomal recessive hypophosphatemic rickets (ARHR). This study investigates the effects of Pi repletion and bone-specific deletion of Fgf23 on bone and mineral metabolism in the dentin matrix protein 1-knockout (Dmp1KO) mouse model of ARHR. At 12 weeks, Dmp1KO mice showed increased serum FGF23 and parathyroid hormone levels, hypophosphatemia, impaired growth, rickets, and osteomalacia. Six weeks of dietary Pi supplementation exacerbated FGF23 production, hyperparathyroidism, renal Pi excretion, and osteomalacia. In contrast, osteocyte-specific deletion of Fgf23 resulted in a partial correction of FGF23 excess, which was sufficient to fully restore serum Pi levels but only partially corrected the bone phenotype. In vitro, we show that FGF23 directly impaired osteoprogenitors' differentiation and that DMP1 deficiency contributed to impaired mineralization independent of FGF23 or Pi levels. In conclusion, FGF23-induced hypophosphatemia is only partially responsible for the bone defects observed in Dmp1KO mice. Our data suggest that combined DMP1 repletion and FGF23 blockade could effectively correct ARHR-associated mineral and bone disorders.
Topics: Animals; Mice; Calcification, Physiologic; Extracellular Matrix Proteins; Familial Hypophosphatemic Rickets; Fibroblast Growth Factors; Hypophosphatemia; Mice, Knockout; Minerals; Osteomalacia
PubMed: 37943605
DOI: 10.1172/jci.insight.156850