scholarly journals The Cell Origin and Role of Osteoclastogenesis and Osteoblastogenesis in Vascular Calcification

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenhong Jiang ◽  
Zhanman Zhang ◽  
Yaodong Li ◽  
Chuanzhen Chen ◽  
Han Yang ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Arterial Calcification ◽  
Arterial Walls ◽  
Large Numbers ◽  
Bone Matrix Proteins ◽  
A Cell ◽  
Mineral Resorption

Arterial calcification refers to the abnormal deposition of calcium salts in the arterial wall, which results in vessel lumen stenosis and vascular remodeling. Studies increasingly show that arterial calcification is a cell mediated, reversible and active regulated process similar to physiological bone mineralization. The osteoblasts and chondrocytes-like cells are present in large numbers in the calcified lesions, and express osteogenic transcription factor and bone matrix proteins that are known to initiate and promote arterial calcification. In addition, osteoclast-like cells have also been detected in calcified arterial walls wherein they possibly inhibit vascular calcification, similar to the catabolic process of bone mineral resorption. Therefore, tilting the balance between osteoblast-like and osteoclast-like cells to the latter maybe a promising therapeutic strategy against vascular calcification. In this review, we have summarized the current findings on the origin and functions of osteoblast-like and osteoclast-like cells in the development and progression of vascular progression, and explored novel therapeutic possibilities.

Nanomechanics of Knockout Mouse Bones

2006 ◽  
Vol 975 ◽  
Author(s):  
N Beril Kavukcuoglu ◽  
Adrian B. Mann
Keyword(s):  
Mechanical Properties ◽  
Knockout Mice ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Wild Type ◽  
Knock Out ◽  
Bone Matrix Proteins ◽  
Fibrillin 1 ◽  
Deficient Mice ◽  
Radial Axis

ABSTRACTOsteocalcin (OC) and osteopontin (OPN) are among the most abundant non-collagenous bone matrix proteins. Both have drawn interest from investigators studying their function in osteoporosis and it is known that mutations of these proteins can also have dramatic effects on the properties of bone. Other proteins including fibrillin 1 and 2 (FBN2) have been less widely studied, but can be mutated in some individuals resulting in connective tissue disorders. It has been reported that abnormal fibrillin may play a role in decreased bone mass. In this study bones from osteopontin (OPN), osteocalcin (OC) and fibrillin-2 (FBN2) knockout mice have been investigated. The study has identified how these proteins affect the bone's nanomechanical properties (hardness and elastic modulus). Nanoindentation tests were performed on the radial axis of cortical femora bones from the knockout mice and their wildtype controls. The results showed that young (age< 12 weeks) OPN knock-out bones have significantly lower mechanical properties than wild-type bones indicate a crucial role for OPN in early bone mineralization. After 12 weeks of age, the OPN knockout and wild-type control bones did not show any statistical difference. In OC deficient mice the mechanical properties were found to increase in the cortical mid-shaft of femora from 1 year old mice, suggesting an increase in bone mineralization, but 3 month old FBN2 deficient mice bones showed a decrease in mechanical properties across the cortical radial axis of the mid- femora.

Effects of Osteopontin Deficiency and Aging on Nanomechanics of Mouse Bone

2004 ◽  
Vol 841 ◽  
Author(s):  
B. Kavukcuoglu ◽  
C. West ◽  
D. T. Denhardt ◽  
A. B. Mann
Keyword(s):  
Mechanical Properties ◽  
Elastic Modulus ◽  
Standard Deviation ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Age Groups ◽  
Matrix Proteins ◽  
Significant Difference ◽  
Bone Matrix Proteins ◽  
New Treatments

ABSTRACTOsteopontin (OPN), a phosphorylated glycoprotein, is among the most abundant non-collageneous bone matrix proteins produced by osteoblasts and osteoclasts. OPN has been implicated in bone formation, resorption and remodeling. However, previous studies have presented contradictory results regarding the effect of OPN on the mechanics and microstructure of bone. This study has used nanoindentation to identify local variations in elastic modulus and hardness of OPN deficient (OPN -/-) and wild-type control (OPN+/+) mouse bones. Specifically, the study has looked at changes in the mechanical properties of OPN-/- and OPN+/+ mouse bones with the mouse's age. Cortical sections of femurs from different age groups ranging from 3 weeks to 58 weeks were tested and compared. The results suggest that there are large, abrupt variations in mechanical properties across the femur's radial section for 3-week-old mouse bone. The hardness (H) drops significantly towards the inner and outer sections so the cortical bone has a mean H=3.66 GPa with a standard deviation of 2.44 GPa. In contrast, the hardness of the 58-week-old mouse bone had a standard deviation of 0.35 GPa and a mean H=1.45 GPa. The hardness across the radial axis of the 58-week-old bone was found to be quite uniform. The elastic modulus showed similar variations to the hardness with respect to age and position on the bone. We conclude that the mechanical properties of the mouse bones decrease substantially with maturity, and statistically the hardness and elastic modulus are more uniform in mature bones than young ones. Surprisingly we found a similar variation in both OPN-/- and OPN+/+ bones, with no statistically significant difference in the mechanical properties of the OPN -/- and OPN+/+ bones. The results for OPN-/- and OPN+/+ mouse bones are particularly important as control of OPN activity has been postulated as a potential treatment for bone pathologies that exhibit a change in the bone mineralization, such as osteoporosis, osteopetrosis and Paget's disease. Understanding the effects of OPN on bone mechanics is a vital step in the development of these new treatments.

Effects of Osteopontin Deficiency and Aging on Nanomechanics of Mouse Bone

2004 ◽  
Vol 844 ◽  
Author(s):  
B. Kavukcuoglu ◽  
C. West ◽  
D.T. Denhardt ◽  
A. B. Mann
Keyword(s):  
Mechanical Properties ◽  
Elastic Modulus ◽  
Standard Deviation ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Age Groups ◽  
Matrix Proteins ◽  
Significant Difference ◽  
Bone Matrix Proteins ◽  
New Treatments

ABSTRACTOsteopontin (OPN), a phosphorylated glycoprotein, is among the most abundant non-collageneous bone matrix proteins produced by osteoblasts and osteoclasts. OPN has been implicated in bone formation, resorption and remodeling. However, previous studies have presented contradictory results regarding the effect of OPN on the mechanics and microstructure of bone. This study has used nanoindentation to identify local variations in elastic modulus and hardness of OPN deficient (OPN -/-) and wild-type control (OPN+/+) mouse bones. Specifically, the study has looked at changes in the mechanical properties of OPN-/- and OPN+/+ mouse bones with the mouse's age. Cortical sections of femurs from different age groups ranging from 3 weeks to 58 weeks were tested and compared. The results suggest that there are large, abrupt variations in mechanical properties across the femur's radial section for 3-week-old mouse bone. The hardness (H) drops significantly towards the inner and outer sections so the cortical bone has a mean H=3.66 GPa with a standard deviation of 2.44 GPa. In contrast, the hardness of the 58-week-old mouse bone had a standard deviation of 0.35 GPa and a mean H=1.45 GPa. The hardness across the radial axis of the 58-week-old bone was found to be quite uniform. The elastic modulus showed similar variations to the hardness with respect to age and position on the bone. We conclude that the mechanical properties of the mouse bones decrease substantially with maturity, and statistically the hardness and elastic modulus are more uniform in mature bones than young ones. Surprisingly we found a similar variation in both OPN-/- and OPN+/+ bones, with no statistically significant difference in the mechanical properties of the OPN -/- and OPN+/+ bones. The results for OPN-/- and OPN+/+ mouse bones are particularly important as control of OPN activity has been postulated as a potential treatment for bone pathologies that exhibit a change in the bone mineralization, such as osteoporosis, osteopetrosis and Paget's disease. Understanding the effects of OPN on bone mechanics is a vital step in the development of these new treatments.

scholarly journals Osteoprotegerin Reverses Osteoporosis by Inhibiting Endosteal Osteoclasts and Prevents Vascular Calcification by Blocking a Process Resembling Osteoclastogenesis

2000 ◽  
Vol 192 (4) ◽  
pp. 463-474 ◽  
Author(s):  
Hosung Min ◽  
Sean Morony ◽  
Ildiko Sarosi ◽  
Colin R. Dunstan ◽  
Casey Capparelli ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Intravenous Injection ◽  
Arterial Calcification ◽  
Osteoporotic Bone ◽  
Arterial Walls ◽  
Adult Mice ◽  
Receptor Activator ◽  
Physiological Calcification ◽  
Rank Signaling ◽  
Bone Elongation

High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG−/2 mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG−/− mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG−/− mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-κB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG−/− mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population.

scholarly journals Do ASARM peptides play a role in nephrogenic systemic fibrosis?

2015 ◽  
Vol 309 (9) ◽  
pp. F764-F769 ◽  
Author(s):  
Peter S. N. Rowe ◽  
Lesya V. Zelenchuk ◽  
Jennifer S. Laurence ◽  
Phil Lee ◽  
William M. Brooks ◽  
...  
Keyword(s):  
Nephrogenic Systemic Fibrosis ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Hypophosphatemic Rickets ◽  
Bone Matrix Proteins ◽  
Risk Of Disease ◽  
Asarm Peptide

Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium (Gd3+)-based contrast agents (GBCAs) in patients with kidney disease. The release of toxic Gd3+ from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of Gd3+ release from GBCAs is unknown. Increased Acidic Serine Aspartate Rich MEPE-associated peptides (ASARM peptides) induce bone mineralization abnormalities and contribute to renal phosphate-handling defects in inherited hypophosphatemic rickets and tumor-induced osteomalacia. The proteolytic cleavage of related bone matrix proteins with ASARM motifs results in release of ASARM peptide into bone and circulation. ASARM peptides are acidic, reactive, phosphorylated inhibitors of mineralization that bind Ca2+ and hydroxyapatite. Since the ionic radius of Gd3+ is close to that of Ca2+, we hypothesized that ASARM peptides increase the risk of NSF by inducing release of Gd3+ from GBCAs. Here, we show 1) ASARM peptides bind and induce release of Gd3+ from GBCAs in vitro and in vivo; 2) A bioengineered peptide (SPR4) stabilizes the Gd3+-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA-induced NSF-like pathology in a murine model with increased ASARM peptide (Hyp mouse). We conclude ASARM peptides may play a role in NSF and SPR4 peptide is a candidate adjuvant for preventing or reducing risk of disease.

scholarly journals Altered distribution of bone matrix proteins and defective bone mineralization in klotho-deficient mice

Bone ◽  
2013 ◽  
Vol 57 (1) ◽  
pp. 206-219 ◽  
Author(s):  
Muneteru Sasaki ◽  
Tomoka Hasegawa ◽  
Tamaki Yamada ◽  
Hiromi Hongo ◽  
Paulo Henrique Luiz de Freitas ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Bone Matrix Proteins ◽  
Defective Bone ◽  
Deficient Mice

Abstract P298: Association of Serum Sclerostin with Vascular Calcification in African Ancestry Men

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Allison L Kuipers ◽  
Iva Miljkovic ◽  
J Jeffery Carr ◽  
James G Terry ◽  
Cara S Nestlerode ◽  
...  
Keyword(s):  
Kidney Function ◽  
Vascular Calcification ◽  
Bone Mineralization ◽  
African Ancestry ◽  
Arterial Calcification ◽  
Serum Samples ◽  
Cross Sectional ◽  
P Values ◽  
Logistic Regression Models ◽  
Health History

Objective: Sclerostin, a Wnt pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in African ancestry men on the island of Tobago. Methods: Detailed health history, clinical exam and computed tomography scans of CAC and AAC were obtained in 191 men aged ≥40 years (mean(SD): 62.9(8.0)years) recruited without regard to health status. Fasting serum samples were drawn and stored at -80°C until time of assay. Serum sclerostin levels were measured using ELISA according to manufacturer’s protocol (Biomedica Gruppe, Vienna, Austria). Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification. Results: In unadjusted analyses, the 57 of 191 (29.8%) of men with CAC were older, more likely to be hypertensive, had lower kidney function and had greater serum sclerostin (all P-values<0.05). The 131 of 191 (68.6%) of men with AAC were also older and more likely to be hypertensive, but they had greater total body fat and were more likely to be on statins, as well (all P-values<0.05). Mean(SD) sclerostin was 45.2 pmol/l (15.6 pmol/l). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with 1.61-times (95%CI 1.02-2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model. Conclusions: This is the first study to show that, among African ancestry men, greater serum sclerostin levels were associated with CAC. In addition to its known role in bone mineralization, the Wnt antagonist, sclerostin, may also play a role in calcification of the coronary arteries.

scholarly journals Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein–deficient Mice

2002 ◽  
Vol 196 (8) ◽  
pp. 1047-1055 ◽  
Author(s):  
Mei Y. Speer ◽  
Marc D. McKee ◽  
Robert E. Guldberg ◽  
Lucy Liaw ◽  
Hsueh-Ying Yang ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Dry Weight ◽  
Inhibitory Effect ◽  
Matrix Gla Protein ◽  
Mutant Mice ◽  
Arterial Calcification ◽  
Ectopic Calcification ◽  
Lineage Markers

Osteopontin (OPN) is abundantly expressed in human calcified arteries. To examine the role of OPN in vascular calcification, OPN mutant mice were crossed with matrix Gla protein (MGP) mutant mice. Mice deficient in MGP alone (MGP−/− OPN+/+) showed calcification of their arteries as early as 2 weeks (wk) after birth (0.33 ± 0.01 mmol/g dry weight), and the expression of OPN in the calcified arteries was greatly up-regulated compared with MGP wild-types. OPN accumulated adjacent to the mineral and colocalized to surrounding cells in the calcified media. Cells synthesizing OPN lacked smooth muscle (SM) lineage markers, SM α-actin and SM22α. However, most of them were not macrophages. Importantly, mice deficient in both MGP and OPN had twice as much arterial calcification as MGP−/− OPN+/+ at 2 wk, and over 3 times as much at 4 wk, suggesting an inhibitory effect of OPN in vascular calcification. Moreover, these mice died significantly earlier (4.4 ± 0.2 wk) than MGP−/− OPN+/+ counterparts (6.6 ± 1.0 wk). The cause of death in these animals was found to be vascular rupture followed by hemorrhage, most likely due to enhanced calcification. These studies are the first to demonstrate a role for OPN as an inducible inhibitor of ectopic calcification in vivo.

Localization of Intracisternal a Particle Antigens in Neoplastic Cells and Preimplantation Mouse Embryos

1980 ◽  
Vol 38 ◽  
pp. 696-697
Author(s):  
Thomas T.F. Huang ◽  
Patricia G. Calarco
Keyword(s):  
Endoplasmic Reticulum ◽  
Normal Development ◽  
Mouse Embryos ◽  
Neoplastic Cells ◽  
Large Numbers ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse ◽  
Intracisternal A Particle ◽  
Normal Feature

The stage specific appearance of a retravirus, termed the Intracisternal A particle (IAP) is a normal feature of early preimplantation development. To date, all feral and laboratory strains of Mus musculus and even Asian species such as Mus cervicolor and Mus pahari express the particles during the 2-8 cell stages. IAP form by budding into the endoplasmic reticulum and appear singly or as groups of donut-shaped particles within the cisternae (fig. 1). IAP are also produced in large numbers in several neoplastic cells such as certain plasmacytomas and rhabdomyosarcomas. The role of IAP, either in normal development or in neoplastic behavior, is unknown.

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