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Pediatric Nephrology (Berlin, Germany) Dec 2015In children with chronic kidney disease (CKD) optimal control of mineral and bone disorder (MBD) is essential not only for the prevention of debilitating skeletal... (Review)
Review
In children with chronic kidney disease (CKD) optimal control of mineral and bone disorder (MBD) is essential not only for the prevention of debilitating skeletal complications and for achieving adequate growth, but also for preserving long-term cardiovascular health. The growing skeleton is particularly vulnerable to the effects of CKD, and bone pain, fractures and deformities are common in children on dialysis. Defective bone mineralisation has been linked with ectopic calcification, which in turn leads to significant morbidity and mortality. Despite national and international guidelines for the management of CKD-MBD, the management of mineral dysregulation in CKD can be extremely challenging, and a significant proportion of patients have calcium, phosphate or parathyroid hormone levels outside the normal ranges. Clinical and experimental studies have shown that, in the setting of CKD, low serum calcium levels are associated with poor bone mineralisation, whereas high serum calcium levels can lead to arterial calcification, even in children. The role of calcium in CKD-MBD is the focus of this review.
Topics: Bone Density; Bone Diseases, Metabolic; Calcification, Physiologic; Calcium; Calcium Phosphates; Child; Humans; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification
PubMed: 25543193
DOI: 10.1007/s00467-014-3017-y -
Journal of Materials Science. Materials... May 2018Osseointegrated implants are frequently used in reconstructive surgery, both in the dental and orthopedic field, restoring physical function and improving the quality of... (Review)
Review
Osseointegrated implants are frequently used in reconstructive surgery, both in the dental and orthopedic field, restoring physical function and improving the quality of life for the patients. The bone anchorage is typically evaluated at micrometer resolution, while bone tissue is a dynamic composite material composed of nanoscale collagen fibrils and apatite crystals, with defined hierarchical levels at different length scales. In order to understand the bone formation and the ultrastructure of the interfacial tissue, analytical strategies needs to be implemented enabling multiscale and multimodal analyses of the intact interface. This paper describes a sample preparation route for successive analyses allowing assessment of the different hierarchical levels of interest, going from macro to nano scale and could be implemented on single samples. Examples of resulting analyses of different techniques on one type of implant surface is given, with emphasis on correlating the length scale between the different techniques. The bone-implant interface shows an intimate contact between mineralized collagen bundles and the outermost surface of the oxide layer, while bone mineral is found in the nanoscale surface features creating a functionally graded interface. Osteocytes exhibit a direct contact with the implant surface via canaliculi that house their dendritic processes. Blood vessels are frequently found in close proximity to the implant surface either within the mineralized bone matrix or at regions of remodeling.
Topics: Animals; Bone and Bones; Bone-Implant Interface; Calcification, Physiologic; Dental Implantation, Endosseous; Dental Implants; Humans; Materials Testing; Osseointegration; Surface Properties
PubMed: 29736606
DOI: 10.1007/s10856-018-6068-y -
Current Opinion in Pharmacology Jun 2015The beginning of the millennium saw the discovery of a new bone-matrix protein, Matrix Extracellular PhosphoglycoprotEin (MEPE) and an associated C-terminal motif called... (Review)
Review
The beginning of the millennium saw the discovery of a new bone-matrix protein, Matrix Extracellular PhosphoglycoprotEin (MEPE) and an associated C-terminal motif called ASARM. This motif and other distinguishing features occur in a group of proteins called SIBLINGs. These proteins include dentin matrix protein 1 (DMP1), osteopontin, dentin-sialophosphoprotein (DSPP), statherin, bone sialoprotein (BSP) and MEPE. MEPE, DMP1 and ASARM-motifs regulate expression of a phosphate regulating cytokine FGF23. Further, a trimeric interaction between phosphate regulating endopeptidase homolog X-linked (PHEX), DMP1, and α5β3-integrin that occurs on the plasma-membrane of the osteocyte mediates FGF23 regulation (FAP pathway). ASARM-peptides competitively inhibit the trimeric complex and increase FGF23. A second pathway involves specialized structures, matrix vesicles pathway (MVP). This review will discuss the FAP and MVP pathways and present a unified model for mineral and energy metabolism.
Topics: Animals; Bone and Bones; Calcification, Physiologic; Energy Metabolism; Extracellular Matrix Proteins; Fibroblast Growth Factor-23; Glycoproteins; Humans; Kidney; Phosphoproteins
PubMed: 25880364
DOI: 10.1016/j.coph.2015.03.006 -
Frontiers of Oral Biology 2016Bone remodeling is a highly coordinated process responsible for bone resorption and formation. It is initiated and modulated by a number of factors including... (Review)
Review
Bone remodeling is a highly coordinated process responsible for bone resorption and formation. It is initiated and modulated by a number of factors including inflammation, changes in hormonal levels and lack of mechanical stimulation. Bone remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix through osteoblasts that subsequently becomes mineralized. In addition to the traditional bone cells (osteoclasts, osteoblasts and osteocytes) that are necessary for bone remodeling, several immune cells such as polymorphonuclear neutrophils, B cells and T cells have also been implicated in bone remodelling. Through the receptor activator of nuclear factor-x03BA;B/receptor activator of the NF-x03BA;B ligand/osteoprotegerin system the process of bone resorption is initiated and subsequent formation is tightly coupled. Mediators such as prostaglandins, interleukins, chemokines, leukotrienes, growth factors, wnt signalling and bone morphogenetic proteins are involved in the regulation of bone remodeling. We discuss here cells and mediators involved in the cellular and molecular machanisms of bone resorption and bone formation.
Topics: Bone Remodeling; Bone Resorption; Calcification, Physiologic; Humans; Inflammation Mediators; Lymphocytes; Neutrophils; Osteoblasts; Osteoclasts; Osteogenesis
PubMed: 26599113
DOI: 10.1159/000351895 -
Advanced Healthcare Materials Mar 2016The need to quantify physicochemical properties of mineralization spans many fields. Clinicians, mineralization researchers, and bone tissue bioengineers need to be able... (Review)
Review
The need to quantify physicochemical properties of mineralization spans many fields. Clinicians, mineralization researchers, and bone tissue bioengineers need to be able to measure the distribution, quantity, and the mechanical and chemical properties of mineralization within a wide variety of substrates from injured muscle to electrospun polymer scaffolds and everything in between. The techniques available to measure these properties are highly diverse in terms of their complexity and utility. Therefore it is of the utmost importance that those who intend to use them have a clear understanding of the advantages and disadvantages of each technique and its appropriateness to their specific application. This review provides all of this information for each technique and uses heterotopic ossification and engineered bone substitutes as examples to illustrate how these techniques have been applied. In addition, we provide novel data using advanced techniques to analyze human samples of combat related heterotopic ossification.
Topics: Bioengineering; Calcification, Physiologic; Chemical Phenomena; Diagnostic Imaging; Humans; Multimodal Imaging; Translational Research, Biomedical
PubMed: 26789418
DOI: 10.1002/adhm.201500617 -
International Journal of Molecular... Sep 2021Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue,... (Review)
Review
Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity.
Topics: Bone Density; Bone Development; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Calcification, Physiologic; Extracellular Matrix Proteins; Fractures, Bone; Humans; Metabolic Networks and Pathways; Mutation; Signal Transduction
PubMed: 34638624
DOI: 10.3390/ijms221910281 -
Advanced Healthcare Materials Feb 2021Biomineralization of skeletal components (e.g., bone and teeth) is generally accepted to occur under strict cellular regulation, leading to mineral-organic composites... (Review)
Review
Biomineralization of skeletal components (e.g., bone and teeth) is generally accepted to occur under strict cellular regulation, leading to mineral-organic composites with hierarchical structures and properties optimized for their designated function. Such cellular regulation includes promoting mineralization at desired sites as well as inhibiting mineralization in soft tissues and other undesirable locations. In contrast, pathological mineralization, with potentially harmful health effects, can occur as a result of tissue or metabolic abnormalities, disease, or implantation of certain biomaterials. This progress report defines mineralization pathway components and identifies the commonalities (and differences) between physiological (e.g., bone remodeling) and pathological calcification formation pathways, based, in part, upon the extent of cellular control within the system. These concepts are discussed in representative examples of calcium phosphate-based pathological mineralization in cancer (breast, thyroid, ovarian, and meningioma) and in cardiovascular disease. In-depth mechanistic understanding of pathological mineralization requires utilizing state-of-the-art materials science imaging and characterization techniques, focusing not only on the final deposits, but also on the earlier stages of crystal nucleation, growth, and aggregation. Such mechanistic understanding will further enable the use of pathological calcifications in diagnosis and prognosis, as well as possibly provide insights into preventative treatments for detrimental mineralization in disease.
Topics: Bone Remodeling; Bone and Bones; Calcification, Physiologic; Calcinosis; Human Body; Humans
PubMed: 33274854
DOI: 10.1002/adhm.202001271 -
Bone May 2023FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this...
FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this study, we reported a novel mechanism of how bone development is regulated by FBXO11. FBXO11 gene knockdown by lentiviral transduction in mouse pre-osteoblast MC3T3-E1 cells leads to reduced osteogenic differentiation, while overexpressing FBXO11 accelerates their osteogenic differentiation in vitro. Furthermore, we generated two osteoblastic-specific FBXO11 conditional knockout mouse models, Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO mice. In both conditional FBXO11KO mouse models, we found FBXO11 deficiency inhibits normal bone growth, in which the osteogenic activity in FBXO11cKO mice is reduced, while osteoclastic activity is not significantly changed. Mechanistically, we found FBXO11 deficiency leads to Snail1 protein accumulation in osteoblasts, leading to suppression of osteogenic activity and inhibition of bone matrix mineralization. FBXO11 knockdown in MC3T3-E1 cells reduced Snail1 protein ubiquitination and increased Snail1 protein accumulation in the cells, which eventually inhibited osteogenic differentiation. In conclusion, FBXO11 deficiency in osteoblasts inhibits bone formation through Snail1 accumulation, inhibiting osteogenic activity and bone mineralization.
Topics: Animals; Mice; Osteogenesis; Cell Differentiation; Calcification, Physiologic; Osteoclasts; Osteoblasts
PubMed: 36863499
DOI: 10.1016/j.bone.2023.116709 -
Journal of the Royal Society, Interface Oct 2016Polar and charged amino acids (AAs) are heavily expressed in non-collagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we... (Review)
Review
Polar and charged amino acids (AAs) are heavily expressed in non-collagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we review what is known on the effect of single AAs on HA precipitation. Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and phosphoserine are largely expressed in NCPs and play a critical role in controlling HA nucleation and growth. Positively charged ones such as arginine (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular matrix proteins such as collagen. Glu, Arg and Lys intake can also increase bone mineral density by stimulating growth hormone production. In vitro studies suggest that the role of AAs in controlling HA precipitation is affected by their mobility. While dissolved AAs are able to inhibit HA precipitation and growth by chelating Ca and PO ions or binding to nuclei of calcium phosphate and preventing their further growth, AAs bound to surfaces can promote HA precipitation by attracting Ca and PO ions and increasing the local supersaturation. Overall, the effect of AAs on HA precipitation is worth being investigated more, especially under conditions closer to the physiological ones, where the presence of other factors such as collagen, mineralization inhibitors, and cells heavily influences HA precipitation. A deeper understanding of the role of AAs in HA mineralization will increase our fundamental knowledge related to bone formation, and could lead to new therapies to improve bone regeneration in damaged tissues or cure pathological diseases caused by excessive mineralization in tissues such as cartilage, blood vessels and cardiac valves.
Topics: Amino Acids; Animals; Bone Density; Calcification, Physiologic; Durapatite; Extracellular Matrix; Humans; Models, Biological
PubMed: 27707904
DOI: 10.1098/rsif.2016.0462 -
Scientific Reports Jan 2018Tough natural nanocomposites like bone, nacre and sea sponges contain within their hierarchy, a mineral (phosphate, silicate or carbonate) phase that interacts with an...
Tough natural nanocomposites like bone, nacre and sea sponges contain within their hierarchy, a mineral (phosphate, silicate or carbonate) phase that interacts with an organic phase. In bone, the role of mineral ultrastructure (organization, morphology, composition) is crucial to the mechanical and biological properties of the tissue. Better understanding of mineral interaction with the organic matrix, in particular non-collagenous proteins, osteocalcin (OC) and osteopontin (OPN), can lead to better design of biomimetic materials. Using small angle x-ray scattering (SAXS) and wavelength dispersive spectroscopy (WDS) on single (OC and OPN) and double (OC-OPN) genetic knockout mice bones, we demonstrate that both osteocalcin and osteopontin have specific roles in the biomolecular regulation of mineral in bone and together they are major determinants of the quality of bone mineral. Specifically, for the first time, we show that proteins osteocalcin and osteopontin regulate bone mineral crystal size and organization in a codependent manner, while they independently determine crystal shape. We found that OC is more dominant in the regulation of the physical properties of bone mineral, while OPN is more dominant in the regulation of the mineral composition.
Topics: Animals; Bone and Bones; Calcification, Physiologic; Genotype; Mice; Mice, Knockout; Minerals; Models, Biological; Osteocalcin; Osteopontin; Scattering, Small Angle; Trace Elements; X-Ray Diffraction
PubMed: 29352125
DOI: 10.1038/s41598-018-19253-w