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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 -
The Journal of Clinical Investigation Feb 2016Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and...
Osteoblast-derived VEGF is important for bone development and postnatal bone homeostasis. Previous studies have demonstrated that VEGF affects bone repair and regeneration; however, the cellular mechanisms by which it works are not fully understood. In this study, we investigated the functions of osteoblast-derived VEGF in healing of a bone defect. The results indicate that osteoblast-derived VEGF plays critical roles at several stages in the repair process. Using transgenic mice with osteoblast-specific deletion of Vegfa, we demonstrated that VEGF promoted macrophage recruitment and angiogenic responses in the inflammation phase, and optimal levels of VEGF were required for coupling of angiogenesis and osteogenesis in areas where repair occurs by intramembranous ossification. VEGF likely functions as a paracrine factor in this process because deletion of Vegfr2 in osteoblastic lineage cells enhanced osteoblastic maturation and mineralization. Furthermore, osteoblast- and hypertrophic chondrocyte-derived VEGF stimulated recruitment of blood vessels and osteoclasts and promoted cartilage resorption at the repair site during the periosteal endochondral ossification stage. Finally, osteoblast-derived VEGF stimulated osteoclast formation in the final remodeling phase of the repair process. These findings provide a basis for clinical strategies to improve bone regeneration and treat defects in bone healing.
Topics: Animals; Bone Regeneration; Calcification, Physiologic; Cell Differentiation; Mice; Mice, Knockout; Osteoblasts; Osteogenesis; Vascular Endothelial Growth Factor A
PubMed: 26731472
DOI: 10.1172/JCI82585 -
Molecular Medicine Reports May 2019Vitamin K2 likely exerts its protective effects during osteoporosis by promoting osteoblast differentiation and mineralization. However, the precise mechanism remains to...
Vitamin K2 likely exerts its protective effects during osteoporosis by promoting osteoblast differentiation and mineralization. However, the precise mechanism remains to be fully elucidated. Autophagy maintains cell homeostasis by breaking down and eliminating damaged proteins and organelles. Increasing evidence in recent years has implicated autophagy in the development of osteoporosis. The aim of the present study was to verify whether vitamin K2 (VK2) can induce autophagy during the differentiation and mineralization of osteoblasts. In the present study, MC3T3‑E1 osteoblasts were treated with various doses of VK2 (10‑8‑10‑3 M) for 1‑5 days. The results revealed no cytotoxicity at concentrations below 10‑5 M, but cell viability was reduced in a dose‑dependent manner at concentrations above 10‑5 M. Furthermore, MC3T3‑E1 osteoblasts were seeded in 6‑well plates in complete medium supplemented with dexamethasone, β‑glycerophosphate and vitamin C (VC) for osteogenic differentiation. MC3T3‑E1 osteoblasts treated with different concentrations (10‑5, 10‑6 and 10‑7 M) of VK2 for 24 h on days 1, 3, 5 and 7 of the differentiation protocol. It was confirmed that VK2 promoted osteoblast differentiation and mineralization by using alkaline phosphatase (ALP) and alizarin red staining. Using western blotting, immunofluorescence, monodansylcadaverine staining and reverse transcription‑quantitative polymerase chain reaction, it was observed that VK2 induced autophagy in osteoblasts. The results revealed that VK2 (1 µM) significantly increased ALP activity and the conversion of microtubule associated protein 1 light chain 3‑α (LC3)II to LC3I in MC3T3‑E1 osteoblasts (P<0.05) at every time point. The number of fluorescent bodies and the intensity increased with VK2, and decreased following treatment with 3‑MA+VK2. There was an increase in the mRNA expression levels of ALP, osteocalcin (OCN) and Runt‑related transcription factor 2 in VK2‑treated cells (P<0.01). The present study further confirmed the association between autophagy and osteoblast differentiation and mineralization through treatment with an autophagy inhibitor [3‑methyladenine (3‑MA)]. Osteoblasts treated with 3‑MA exhibited significant inhibition of ALP activity and osteogenic differentiation (both P<0.05). In addition, ALP activity and osteogenesis in the VK2+3‑MA group was lower compared with VK2‑treated cells (P<0.05 for both). The present study confirmed that VK2 stimulated autophagy in MC3T3 cells to promote differentiation and mineralization, which may be a potential therapeutic target for osteoporosis.
Topics: Animals; Autophagy; Calcification, Physiologic; Cell Differentiation; Cell Line; Cell Survival; Mice; Osteoblasts; Osteogenesis; Vitamin K 2
PubMed: 30896842
DOI: 10.3892/mmr.2019.10040 -
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 -
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 -
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 -
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 -
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 -
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