scholarly journals DSPP effects on in vivo bone mineralization

Bone ◽  
2008 ◽  
Vol 43 (6) ◽  
pp. 983-990 ◽  
Author(s):  
Kostas Verdelis ◽  
Yunfeng Ling ◽  
Taduru Sreenath ◽  
Naoto Haruyama ◽  
Mary MacDougall ◽  
...  
Keyword(s):  
Bone Mineralization

scholarly journals Matrix Vesicles: Role in Bone Mineralization and Potential Use as Therapeutics

2021 ◽  
Vol 14 (4) ◽  
pp. 289
Author(s):  
Sana Ansari ◽  
Bregje W. M. de de Wildt ◽  
Michelle A. M. Vis ◽  
Carolina E. de de Korte ◽  
Keita Ito ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Cells ◽  
Bone Mineralization ◽  
Recipient Cell ◽  
Organic Matrix ◽  
Matrix Vesicles ◽  
Matrix Mineralization

Bone is a complex organ maintained by three main cell types: osteoblasts, osteoclasts, and osteocytes. During bone formation, osteoblasts deposit a mineralized organic matrix. Evidence shows that bone cells release extracellular vesicles (EVs): nano-sized bilayer vesicles, which are involved in intercellular communication by delivering their cargoes through protein–ligand interactions or fusion to the plasma membrane of the recipient cell. Osteoblasts shed a subset of EVs known as matrix vesicles (MtVs), which contain phosphatases, calcium, and inorganic phosphate. These vesicles are believed to have a major role in matrix mineralization, and they feature bone-targeting and osteo-inductive properties. Understanding their contribution in bone formation and mineralization could help to target bone pathologies or bone regeneration using novel approaches such as stimulating MtV secretion in vivo, or the administration of in vitro or biomimetically produced MtVs. This review attempts to discuss the role of MtVs in biomineralization and their potential application for bone pathologies and bone regeneration.

scholarly journals Inhibition of Fibroblast Growth Factor-23 (FGF-23) As a Novel Strategy to Target Bone and Hematopoietic Stem Cell Niche Defects in Beta-Thalassemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-2
Author(s):  
Annamaria Aprile ◽  
Laura Raggi ◽  
Mariangela Storto ◽  
Isabella Villa ◽  
Sarah Marktel ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Fibroblast Growth Factor 23 ◽  
Beta Thalassemia ◽  
Causative Role ◽  
Ineffective Erythropoiesis ◽  
Hematopoietic Stem ◽  
Bm Niche ◽  
Fgf 23

In the last decade many studies unraveled the bone marrow (BM) niche regulation and crosstalk with hematopoietic stem cells (HSC) in steady state conditions and malignancies, but HSC-niche interactions are still underexplored in hematological inherited disorders. We have recently provided the first demonstration of impaired HSC function caused by an altered BM niche in a non-malignant disease, beta-thalassemia (BT) (Aprile et al., Blood 2020). BT is a congenital hemoglobin disorder resulting in severe anemia, ineffective erythropoiesis and multi-organ secondary complications, such as bone defects. It is one of the most globally widespread monogenic diseases, which can be cured by transplantation of HSC from compatible healthy donors or autologous HSC from patients upon gene therapy. Cases of graft failure have been reported, but causes have not been deeply investigated and might include an impaired HSC function and a defective supporting activity of the BM niche, worsened by age and disease progression. We showed that the prolonged residence of HSC into an altered BM stromal niche in BT Hbbth3/+ (th3) mice negatively affects stem cell number, quiescence and self-renewal. Moreover, we demonstrated that correction of HSC-stromal niche crosstalk rescues BT HSC function by in vivo reactivation of parathyroid hormone (PTH) signaling. Consistently with the common finding of osteoporosis in BT patients, we found reduced bone deposition and low levels of PTH also in the murine model. We investigated the potential mechanisms underlying the decreased PTH and bone defect and we focused on the role of fibroblast growth factor-23 (FGF-23). FGF-23 is a systemic hormone mainly secreted by osteocytes, which acts as negative regulator of bone metabolism by inhibiting bone mineralization and PTH production by parathyroid glands. Since FGF-23 is positively modulated by the anemia-related factor erythropoietin (EPO), we hypothesized that the high EPO levels in BT, subsequent to ineffective erythropoiesis, might contribute to increase FGF-23. We measured high levels of circulating FGF-23 in th3 mice (wt vs. th3: 399.7±69.77 vs. 1975±209.3 pg/ml, p<0.01) and also in BT patients (HD vs. THAL: 94.2±3.8 vs. 125.8±9.2 RU/ml, p<0.05). To provide proof of concept data of the causative role of FGF-23 on BT bone and stromal niche defects, we inhibited FGF-23 signaling. FGF-23 inhibition by in vivo administration of FGF-23 blocking peptide rescued the bone defect in th3 mice, by increasing trabecular bone mineral density (th3 vs. th3+FGF23inh: 117.7±3.3 vs. 181.1±6.9 mg/cm3, p<0.0001). Importantly, the treatment restored the frequency of HSC to levels comparable to wild-type controls by expanding the pool of quiescent cells (th3 vs. th3+FGF23inh: 0.03±0.002 vs. 0.07±0.0% on Linneg BM cells, p<0.0001). Consistently, we found increased the expression of key molecules by bone cells, such as Jagged-1 and osteopontin, involved in the functional crosstalk between HSC and the stromal niche. Interestingly, FGF-23 inhibition had also a positive anti-apoptotic effect on the expanded BM erythroid compartment, promoting the maturation of erythroid precursors, as already shown in models of secondary anemias. Preliminary evidence in BT patients showed negative correlations between FGF-23 levels and markers of bone homeostasis (e.g. osteocalcin and vitamin D) and positive correlations with makers of ineffective erythropoiesis (e.g. reticulocytes), thus proposing FGF-23 as the molecule at the crossroads of erythropoiesis and bone metabolism in BT. In vivo studies and molecular analysis in th3 mice and patients' samples will better unravel the causative role of EPO on FGF-23 levels in BT and the negative impact of high FGF-23 on bone mineralization and BM stromal niche-HSC interactions. Our findings uncover an underexplored role of FGF-23 in bone and BM niche defects in BT, as a condition of severe anemia and chronic EPO stimulation. The inhibition of FGF-23 signaling might provide a novel strategy to ameliorate bone compartment and restore HSC-BM niche interactions in BT, with a potential translational relevance in improving HSC transplantation approaches. Disclosures Motta: Sanofi Genzyme: Honoraria. Cappellini:BMS: Honoraria; CRISPR Therapeutics, Novartis, Vifor Pharma: Membership on an entity's Board of Directors or advisory committees; Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals LOSS OF PROTEINPOLYSACCHARIDES AT SITES WHERE BONE MINERALIZATION IS INITIATED

1972 ◽  
Vol 20 (4) ◽  
pp. 279-292 ◽  
Author(s):  
D. BAYLINK ◽  
J. WERGEDAL ◽  
E. THOMPSON
Keyword(s):  
Calcium Concentration ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Indirect Evidence ◽  
Experimental Conditions ◽  
Acid Polysaccharide ◽  
Major Acid ◽  
Tibial Cortex

In both ground sections and demineralized frozen sections of the rat tibial cortex, osteoid but not mature bone matrix stained for proteinpolysaccharides with the Alcian Blue and toluidine blue techniques. The loss of proteinpolysaccharide staining occurred precisely at the mineralizing front, which was identified by in vivo lead or procion markers, not only in normal animals but also in animals in which osteoid width was either increasing or decreasing. In vitro, both proteases and saccharidases abolished proteinpolysaccharide staining of osteoid. Critical electrolyte concentration and other procedures indicated that the major acid polysaccharide component in osteoid is chondroitin sulfate. Consistent with these findings, electron microprobe analyses revealed that sulfur concentration was high in osteoid but dropped abruptly as calcium concentration increased at the mineralizing front. The precise synchronization between loss of proteinpolysaccharides and onset of mineralization under various experimental conditions provides strong indirect evidence that the loss of these macromolecules is somehow involved in initiation of mineralization in bone.

scholarly journals Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation

2010 ◽  
Vol 190 (6) ◽  
pp. 1107-1121 ◽  
Author(s):  
Harikiran Nistala ◽  
Sui Lee-Arteaga ◽  
Silvia Smaldone ◽  
Gabriella Siciliano ◽  
Luca Carta ◽  
...  
Keyword(s):  
Bone Formation ◽  
Transforming Growth Factor ◽  
Bone Mineralization ◽  
Bmp Signaling ◽  
Direct Role ◽  
Morphogenetic Protein ◽  
Fibrillin 1 ◽  
Osteoblast Maturation

Extracellular regulation of signaling by transforming growth factor (TGF)–β family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF-β and bone morphogenetic protein (BMP) bioavailability in bone. Fibrillin-2–null (Fbn2−/−) mice display a low bone mass phenotype that is associated with reduced bone formation in vivo and impaired osteoblast maturation in vitro. This Fbn2−/− phenotype is accounted for by improper activation of latent TGF-β that selectively blunts expression of osterix, the transcriptional regulator of osteoblast maturation, and collagen I, the structural template for bone mineralization. Cultured osteoblasts from Fbn1−/− mice exhibit improper latent TGF-β activation as well, but mature faster because of increased availability of otherwise matrix-bound BMPs. Additional in vitro evidence excludes a direct role of microfibrils in supporting mineral deposition. Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-β and BMP signaling.

scholarly journals DMP1 Depletion Decreases Bone Mineralization In Vivo: An FTIR Imaging Analysis

2005 ◽  
Vol 20 (12) ◽  
pp. 2169-2177 ◽  
Author(s):  
Yunfeng Ling ◽  
Hector F Rios ◽  
Elizabeth R Myers ◽  
Yongbo Lu ◽  
Jian Q Feng ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Imaging Analysis ◽  
Ftir Imaging

Impact of Biphasic Calcium Phosphate Bioceramics on Osteoporotic Hip Bone Mineralization In Vivo Six Months after Implantation

2016 ◽  
Vol 721 ◽  
pp. 229-233 ◽  
Author(s):  
Sandris Petronis ◽  
Janis Locs ◽  
Vita Zalite ◽  
Mara Pilmane ◽  
Andrejs Skagers ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Tricalcium Phosphate ◽  
Biphasic Calcium Phosphate ◽  
Bone Mineralization ◽  
Bone Substitutes ◽  
Tissue Response ◽  
Control Group ◽  
Osteoporotic Bone ◽  
Local Recovery

Calcium bone substitutes are successfully used for local recovery of osteoporotic bone and filling of bone defects. Previous studies revieled that biphasic calcium phosphate (BCP) show better bioactivity in compare to pure β-tricalcium phosphate or hydroxyapatite. Also increased porosity of material promotes better bone tissue response. Aim of this experiment was to evaluate immunohistologically response of osteoporotic bone of experimental animal to implantation of granules with hydroxyapatite/β-tricalcium phosphate (HAp/β-TCP) ratio of 90/10. Calcium phosphate (CaP) was synthesized by aqueous precipitation technique from calcium hydroxide and phosphoric acid. Bioceramic granules in size range from 1.0 to 1.4 mm were prepared with nanopore sizes around 200 nm. We used nine female rabbits with induced osteoporosis in this experiment. Six animals in study group underwent implantation of BCP in hip bone defect and three animals in control group left without BCP implantation. After 6 months animals were euthanized, bone samples collected and proceeded for detection of bone activity and repair markers: osteocalcin (OC), osteopontin (OP) and osteoprotegerin (OPG). Controls showed the presence of experimental bone osteoporosis. In experimental group bone showed partially resorbed bioceramic granules and in some samples new bone formation near the granuli was observed. Increase of OC and OPG up to twice as to compare to control group were detected as well. Implantation of BCP granules in osteoporotic rabbit bone increases expression of OC and OPG indicating the activation of osteoblastogenesis and bone mineralization in vivo.

TETRACYCLINE LABELLING OF BONE AND THE ZONE OF DEMARCATION OF OSTEOID SEAMS

1962 ◽  
Vol 40 (1) ◽  
pp. 485-489 ◽  
Author(s):  
Harold M. Frost
Keyword(s):  
Bone Mineralization ◽  
Lamellar Bone ◽  
Tetracycline Antibiotics ◽  
Tetracycline Labelling

In human lamellar bone, mineralization begins in a plane, termed the zone of demarcation, which separates osteoid seams from mineralized bone. Permanently fixed tetracycline antibiotics are deposited in the zone of demarcation in vivo, and in no other locus in lamellar bone.

scholarly journals A comparative study of the effects of genistein, estradiol and raloxifene on the murine skeletal system.

2009 ◽  
Vol 56 (2) ◽  
Author(s):  
Leszek Sliwiński ◽  
Joanna Folwarczna ◽  
Barbara Nowińska ◽  
Urszula Cegieła ◽  
Maria Pytlik ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Marrow ◽  
Mrna Expression ◽  
Bone Marrow Cells ◽  
Bone Mineralization ◽  
Mouse Bone Marrow ◽  
Skeletal System ◽  
Mouse Bone Marrow Cells

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. The aim of the present study was to compare the effects of genistein, estradiol and raloxifene on the skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg) or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium content, macrometric parameters and mechanical properties were examined. Also the effects of genistein, estradiol and raloxifene (10(-9)-10(-7) M) on the formation of osteoclasts from neonatal mouse bone marrow cells and the activity of osteoblasts isolated from neonatal mouse calvariae were compared. In vivo, estrogen deficiency resulted in the impairment of bone mineralization and bone mechanical properties. Raloxifene but not estradiol or genistein improved bone mineralization. Estradiol fully normalized the bone mechanical properties, whereas genistein augmented the deleterious effect of estrogen-deficiency on bone strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This difference may explain the lack of genistein effect on bone mineralization observed in ovariectomized rats in the in vivo study. Concluding, our experiments demonstrated profound differences between the activities of genistein, estradiol and raloxifene towards the osseous tissue in experimental conditions.

scholarly journals Exposure to high levels of magnesium disrupts bone mineralization in vitro and in vivo

2020 ◽  
Vol 8 (21) ◽  
pp. 1419-1419
Author(s):  
Wenxiang Chu ◽  
Tao Li ◽  
Gaozhi Jia ◽  
Yongyun Chang ◽  
Zhiqing Liu ◽  
...  
Keyword(s):  
Bone Mineralization

scholarly journals Androgen Receptor (AR) Pathophysiological Roles in Androgen Related Diseases in Skin, Metabolism Syndrome, Bone/Muscle and Neuron/Immune Systems: Lessons Learned from Mice Lacking AR in Specific Cells

2013 ◽  
Vol 11 (1) ◽  
pp. nrs.11001 ◽  
Author(s):  
Chawnshang Chang ◽  
Shuyuan Yeh ◽  
Soo Ok Lee ◽  
Ta-min Chang
Keyword(s):  
Androgen Receptor ◽  
Mouse Models ◽  
Bone Mineralization ◽  
Muscle Growth ◽  
Lessons Learned ◽  
Specific Cell ◽  
Cell Type ◽  
Vast Number ◽  
Tissue Specific

The androgen receptor (AR) is expressed ubiquitously and plays a variety of roles in a vast number of physiological and pathophysiological processes. Recent studies of AR knockout (ARKO) mouse models, particularly the cell type- or tissue-specific ARKO models, have uncovered many AR cell type- or tissue-specific pathophysiological roles in mice, which otherwise would not be delineated from conventional castration and androgen insensitivity syndrome studies. Thus, the AR in various specific cell types plays pivotal roles in production and maturation of immune cells, bone mineralization, and muscle growth. In metabolism, the ARs in brain, particularly in the hypothalamus, and the liver appear to participate in regulation of insulin sensitivity and glucose homeostasis. The AR also plays key roles in cutaneous wound healing and cardiovascular diseases, including atherosclerosis and abdominal aortic aneurysm. This article will discuss the results obtained from the total, cell type-, or tissue-specific ARKO models. The understanding of AR cell type- or tissue-specific physiological and pathophysiological roles using these in vivo mouse models will provide useful information in uncovering AR roles in humans and eventually help us to develop better therapies via targeting the AR or its downstream signaling molecules to combat androgens/AR-related diseases.

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