Calcification Defects Research Articles

Visible light-induced cross-linking of porcine pericardium for the improvement of endothelialization, anti-tearing, and anticalcification properties.

Population aging and the development of transcatheter aortic valve replacement boost the implantation of bioprosthetic heart valves (BHVs) in patients worldwide. However, the traditional glutaraldehyde cross-linked BHVs fail within 12-15 years mainly due to leaflet tear and calcification defects. In this study, a novel visible light-induced cross-linking of the porcine pericardium (PP) was realized by the photo-oxidation of the furfuryl-modified PP in the presence of Rose Bengal. The resulting material showed comparable collagen stability with the glutaraldehyde cross-linked PP and appropriate biomechanical properties such as tensile strength, modulus, and elongation, suggesting that this material could meet the general requirement for BHVs. Besides, this cross-linked PP showed significantly improved cytocompatibility compared with the Glut-cross-linked PP, with no cytotoxicity to L929 cells and the ability to support HUVECgrowth. Meanwhile, this material showed superior anti-tearing performance and much less calcification than the Glut-cross-linked PP in hope of reducing the risk of BHV failure. Considering these results, the visible light-induced cross-linking method proposed in this study could provide a promising way to construct a biocompatible and robust biomaterial for the fabrication of the BHV.

A New Zebrafish Model for Pseudoxanthoma Elasticum.

Calcification of various tissues is a significant health issue associated with aging, cancer and autoimmune diseases. There are both environmental and genetic factors behind this phenomenon and understanding them is essential for the development of efficient therapeutic approaches. Pseudoxanthoma elasticum (PXE) is a rare genetic disease, a prototype for calcification disorders, resulting from the dysfunction of ABCC6, a transport protein found in the membranes of cells. It is identified by excess calcification in a variety of tissues (e.g., eyes, skin, arteries) and currently it has no cure, known treatments target the symptoms only. Preclinical studies of PXE have been successful in mice, proving the usefulness of animal models for the study of the disease. Here, we present a new zebrafish (Danio rerio) model for PXE. By resolving some ambiguous assemblies in the zebrafish genome, we show that there are two functional and one non-functional paralogs for ABCC6 in zebrafish (abcc6a, abcc6b.1, and abcc6b.2, respectively). We created single and double mutants for the functional paralogs and characterized their calcification defects with a combination of techniques. Zebrafish deficient in abcc6a show defects in their vertebral calcification and also display ectopic calcification foci in their soft tissues. Our results also suggest that the impairment of abcc6b.1 does not affect this biological process.

Micropaleontological study of the Moroccan Mediterranean western coastline foraminifera and their morphological abnormalities

In order to contribute to the identification of the current faunistic composition of the Moroccan Mediterranean western coastline foraminifera, sediment from 4 stations have been analyzed, along with some abiotic parameters (pH, dissolved oxygen, temperature, and salinity), In order to characterize their populations, different Ecological indices were calculated and compared in the various samples. A total of 3451 individuals belonging to 14 species were recognized (90,26% hyaline, 9,74% porcelaneous, and none agglutinated test was found), all assemblages were dominated mainly by Elphidium crispum, Ammonia beccarii, and subordinately by Quinqueloculina sp1 and Heterolepa dutemplei. All sampling sites showed remarkable similarity in the Foraminiferal assemblages, and the Oued Nigro station is considered the wealthiest and densest site, whereas Oued Martil records the lowest values of those parameters. On the other hand, the Sample from M'diq presents the lowest diversity index even if it is the second in terms of density. The faunistic analysis had also allowed the observation of some morphological abnormalities only found in the Oued Nigro station, affecting some individuals' tests. A small-sized chamber mainly manifests the abnormal appearances in the spiral whorls and calcification defects in the calcareous wall.

Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ

Polycystin-1 (PC1), encoded by the PKD1 gene that is mutated in the autosomal dominant polycystic kidney disease, regulates a number of processes including bone development. Activity of the transcription factor RunX2, which controls osteoblast differentiation, is reduced in Pkd1 mutant mice but the mechanism governing PC1 activation of RunX2 is unclear. PC1 undergoes regulated cleavage that releases its C-terminal tail (CTT), which translocates to the nucleus to modulate transcriptional pathways involved in proliferation and apoptosis. We find that the cleaved CTT of PC1 (PC1-CTT) stimulates the transcriptional coactivator TAZ (Wwtr1), an essential coactivator of RunX2. PC1-CTT physically interacts with TAZ, stimulating RunX2 transcriptional activity in pre-osteoblast cells in a TAZ-dependent manner. The PC1-CTT increases the interaction between TAZ and RunX2 and enhances the recruitment of the p300 transcriptional co-regulatory protein to the TAZ/RunX2/PC1-CTT complex. Zebrafish injected with morpholinos directed against pkd1 manifest severe bone calcification defects and a curly tail phenotype. Injection of messenger RNA (mRNA) encoding the PC1-CTT into pkd1-morphant fish restores bone mineralization and reduces the severity of the curly tail phenotype. These effects are abolished by co-injection of morpholinos directed against TAZ. Injection of mRNA encoding a dominant-active TAZ construct is sufficient to rescue both the curly tail phenotype and the skeletal defects observed in pkd1-morpholino treated fish. Thus, TAZ constitutes a key mechanistic link through which PC1 mediates its physiological functions.

SPR4-peptide alters bone metabolism of normal and HYP mice

ContextASARM-peptides are substrates and ligands for PHEX, the gene responsible for X-linked hypophosphatemic rickets (HYP). PHEX binds to the DMP1-ASARM-motif to form a trimeric-complex with α5β3-integrin on the osteocyte surface and this suppresses FGF23 expression. ASARM-peptide disruption of this complex increases FGF23 expression. We used a 4.2kDa peptide (SPR4) that binds to ASARM-peptide and ASARM-motif to study DMP1–PHEX interactions and to assess SPR4 for treating inherited hypophosphatemic rickets. DesignSubcutaneously transplanted osmotic pumps were used to infuse SPR4-peptide or vehicle into wild-type mice (WT) and HYP-mice for 4weeks. ResultsAsymmetrically distributed mineralization defects occurred with WT-SPR4 femurs. Specifically, SPR4 induced negative effects on trabecular bone and increased bone volume and mineralization in cortical-bone. Markedly increased sclerostin and reduced active β-catenin occurred with HYP mice. SPR4-infusion suppressed sclerostin and increased active β-catenin in WT and HYP mice and improved HYP-mice trabecular mineralization defects but not cortical mineralization defects. ConclusionsSPR4-peptide has bimodal activity and acts by: (1) preventing DMP1 binding to PHEX and (2) sequestering an inhibitor of DMP1–PHEX binding, ASARM-peptide. In PHEX defective HYP-mice the second pathway predominates. Although SPR4-peptide improved trabecular calcification defects, decreased sclerostin and increased active β-catenin it did not correct HYP-mice cortical mineralization defects on a normal phosphate diet. Thus, for inherited hypophosphatemic rickets patients on a normal phosphate diet, SPR4-peptide is not a useful therapeutic.

Perspective: Cell–Cell Adhesion and Signaling Through Cadherins: Connecting Bone Cells in Their Microenvironment

Perspective: Cell–Cell Adhesion and Signaling Through Cadherins: Connecting Bone Cells in Their Microenvironment

Pathogenesis of secondary hyperparathyroidism and renal bone disease

Patients with chronic renal disease (CKD)almost always develop secondary hyperparathyroidism (SHPT) due to hypocalcemia, phosphate retention, and abnormalities in vitamin D (VD) metabolism. Concomitant decreases in VD receptor and calcium sensing receptor in the parathyroid glands render them more resistant to the action of VD and calcium, and accelerate parathyroid cell growth. Several types of bone diseases are known to occur in CKD patients. Excessive secretion of parathyroid hormone (PTH) due to SHPT causes high-turnover bone disease, called osteitis fibrosa. Among low-turnover bone disease (LTBD), osteomalacia which is characterized by calcification defect is often complicated with VD deficiency and/or aluminum accumulation. Recently, frequency of adynamic bone disease caused by PTH suppression, another type of LTBD, is increasing probably due to calcium salts as phosphate binder with or without VD treatment.

Relationship between bone fluoride content and histological evidence of calcification defects in osteoporotic women treated long term with sodium fluoride

Fluoride treatment is used to increase bone formation and cancellous bone mass in patients suffering from postmenopausal osteoporosis with vertebral fractures. Patients submitted to similar therapeutic protocols have shown various histological responses to the treatment, some developing calcification defects and others not. In fact, the bone histological response to fluoride salts depends on the cumulative uptake of fluoride by bone. To clarify the relationship between the presence of calcification defects (identified by the presence of mottled bone and linear formation defects) and the bone fluoride content, a retrospective study was performed on 29 women with type 1 osteoporosis and treated for several months (11-24) with sodium fluoride (50 mg/day), calcium and vitamin D. Bone fluoride content always significantly increased after treatment, but it was significantly higher in patients showing calcification defects than in those having no defects. These differences between the two groups of patients were not due to differences in clinical details (no significant differences concerning age, duration of treatment, total amount of fluoride ingested, renal function) or in their bone remodelling activity. Thus, it may be hypothesized that the high bone fluoride uptake is due to different individual responses from one patient to another concerning the bioavailability of the same dose of fluoride. This is difficult to predict, except by testing the individual bioavailability of the compound to be used in each patient before starting long-term treatment.

Teratogenicity of zinc deficiency in the rat: study of the fetal skeleton.

Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. This study identifies fetal skeletal malformations that affect calcified and non-calcified bone tissue as a result of gestational zinc deficiency in rats, and it assesses the effect of maternal ZD in fetal bone calcification. Pregnant Sprague-Dawley rats (180-250 g) were fed 1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), 2) a zinc-deficient diet (0 microgram/g) ad libitum (group ZD), or 3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed. Fetuses were weighed, examined for external malformations, and stained in toto with a double-staining technique for the study of skeletal malformations. Maternal and fetal tissues were used for Zn, Mg, Ca, and P determinations. Gross external malformations were present in 97% of the ZD fetuses. No external malformations were found in fetuses from groups C and PF. Ninety-one percent of cleared ZD fetuses had multiple skeletal malformations, whereas only 3% of the fetuses of group PF had skeletal defects; no skeletal malformations were found in fetuses from group C. Some of the skeletal malformations described in the ZD fetuses, mainly affecting non-calcified bone, were not mentioned in previous reports, thus stressing the importance of using double-staining techniques. Examination of stained fetuses and counting of ossification centers revealed important calcification defects in ZD fetuses. These effects were confirmed by lower Ca and P concentrations in fetal bone with alteration of the Ca:P ratio.

Microdissection-elemental analysis of the mineralizing growth cartilage of the normal and rachitic chick

The concentrations of elements in avian growth cartilage were studied by electron probe x-ray emission microanalysis (EDX). The cartilage was prepared for analysis by freezing, freeze-fracturing, freeze-drying, and carbon coating techniques. Cells and matrix fragments were removed from the tissue by microdissection with a tungsten needle in a scanning electron microscope (SEM) equipped with a real-time stereoscopic viewing facility. The samples were analyzed in the same SEM by EDX. Elemental analyses were performed on each fragment at a distance from the tissue sample, and hence background radiation due to the sample was eliminated. An important finding was that the intracellular potassium concentration of chondrocytes in calcified cartilage was similar to the levels in the premineralized zones. This observation supports the view that chondrocytes do not die in the process of, or as a consequence of, mineralization of the surrounding matrix. Calcium peaks were seen in the matrix at all levels and in chondrocytes immediately prior to mineralization. In contrast, phosphorus levels were always high in cells and low or absent from the premineralized matrix. At the mineralization front the appearance of a phosphorus peak in the matrix just preceded the deposition of mineral. We propose that the transfer of phosphorus from cell to matrix is a rate-limiting step in mineralization. Finally, when rachitic and normal cartilage were compared, little difference was seen in the profile of either intracellular or extracellular elements. However, in rickets the mineralized matrix remained soft in consistency. We suggest that this may reflect a phosphorus-related calcification defect that prevents growth and interlocking of the apatite crystallites.

Case report: Dystrophic calcification, cataracts, and enamel hypoplasia die to long-standing, privational vitamin D deficiency

A 19-year-old Indian girl presenting with intermittent tetany, enamel hypoplasia, bilateral cataracts, and calcification of the basal ganglia is described. Dental evidence suggested a calcification defect had been present from the age of 2–3 years. Hypocalcemia, hyperphosphatemia, and low levels of immunoassayable parathyroid hormone (iPTH), urinary cAMP, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were documented, suggesting hypoparathyroidism with vitamin D deficiency. A bone biopsy showed osteomalacia. Following ultraviolet irradiation and oral calciferol therapy, a symptomatic and biochemical response typical of privational vitamin D deficiency occurred. iPTH levels rose to normal and remained normal following withdrawal of treatment, indicating that the clinical features were entirely due to long-standing vitamin D deficiency.

Autosomal recessive pigmented hypomaturation amelogenesis imperfecta: Report of a kindred

A kindred of amelogenesis imperfecta of the pigmented hypomaturation type confirms the observation that hypomaturation amelogenesis imperfecta occurs both as an autosomal recessively inherited trait and as an X-linked disorder. Histologic sections of enamel show defects in rod structure and voids in enamel rod sheaths which are either empty, filled with an eosinophilic material resembling the thixotropic gel of ameloblasts, or contain a brown pigment. SEM photomicrographs show a fibrous pattern of structureless enamel rods and interprismatic voids. It is suggested that the inability of the ameloblasts to hydrolyze or resorb products of thixotropic gel results in a calcification defect in the enamel rod with accumulation of material at the periphery of Tomes' process, resulting in defects of enamel rod sheath.

Recent Progress in Osteomalacia and Rickets

Review1 December 1967Recent Progress in Osteomalacia and RicketsA. ROBERT ARNSTEIN, M.D., BOY FRAME, M.D., F.A.C.P., HAROLD M. FROST, M.D.A. ROBERT ARNSTEIN, M.D.Search for more papers by this author, BOY FRAME, M.D., F.A.C.P.Search for more papers by this author, HAROLD M. FROST, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-6-1296 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOsteomalacia, including rickets, is a condition of bone characterized by the accumulation of increased amounts of bone matrix (osteoid) and epiphyseal cartilagethat fail to calcify or do so extremely slowly. It represents a systemic disorder of the skeleton that is the end result of calcification defects arising from a variety of causes. Since osteomalacia is encountered under a number of clinically dissimilar circumstances in which its presence is not always obvious, we have reviewed the subject in recent, selected literature with the intent to clarify its diagnosis in morphologic and dynamic terms and to discuss its clinical spectrum with emphasis...

Pseudohypoparathyroidism

A case of pseudohypoparathyrodism has been presented, and the dental findings of pitting hypoplasia of the enamel of permanent teeth have been described. Ground sections indicated that the defect was primarily one of enamel formation and not ascribable to resorption of the fully formed enamel. Microradiographs demonstrated a calcification defect in the dentine, most conspicuous around the abnormal apices of the roots of teeth. A review of the literature indicates that evidence of the genetic transmission of PHP as a sex-linked dominant trait is incomplete. The sharing of clinical and/or chemical features by PHP, PPHP, the hypocalcemia-basal ganglia calcification syndrome, and the basal-cell nevi—odontogenic keratocysts of the jaw syndrome is discussed, and it is suggested that the tendency to develop medulloblastoma may be a related disorder.