Relationships of Viscosity With Contact Hardness and Modulus of Bone Matrix Measured by Nanoindentation

2010 ◽  
Vol 132 (2) ◽  
Author(s):  
Do-Gyoon Kim ◽  
Sarandeep S. Huja ◽  
Hye Ri Lee ◽  
Boon Ching Tee ◽  
Sarah Hueni
Keyword(s):  
Mechanical Stability ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Active Form ◽  
Direct Measure ◽  
Viscoelastic Deformation ◽  
Plastic Properties ◽  
Viscoelastic Creep ◽  
Voigt Model ◽  
Osteonal Bone

Creep is an active form of time-dependent viscoelastic deformation that occurs in bone tissue during daily life. Recent findings indicate bone mineralization, which is involved in determining the elastic and plastic properties of bone matrix, can also contribute in controlling its viscoelastic property. Nanoindentation viscosity was used as a direct measure for the capacity of a material to resist viscous-like flow under loading. The objectives of this study were to examine (1) whether the nanoindentation viscosity obtained using the traditional viscoelastic Voigt model can describe creep response of bone matrix and (2) how the nanoindentation viscosity is related to contact hardness and elastic modulus. The Voigt model accurately described the creep behavior of bone matrix (r2>0.96, p<0.001). The nanoindentation viscosity had strong relationships with nanoindentation contact hardness (r2=0.94, p<0.001) and modulus (r2=0.83, p<0.001) independent of tissue ages of osteonal bone matrix. The strong positive relationships of nanoindentation viscosity with contact hardness and modulus can be interpreted as increases in the mineral portion of bone matrix may limit the interfibril motion of collagen while enhancing the mechanical stability of bone. We suggest that previous nanoindentation results can be reanalyzed to characterize the viscoelastic creep using the Voigt model.

Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

2002 ◽  
pp. 45-59 ◽  
Author(s):  
K W Colston ◽  
C M√∏rk Hansen
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Bone Mineralization ◽  
Active Form ◽  
Cell Types ◽  
Cell Cycle Regulators ◽  
Dihydroxyvitamin D ◽  
Cell Growth And Differentiation ◽  
Regulatory Effects ◽  
Apoptotic Effects

It is now well established that, in addition to its central role in the maintenance of extracellular calcium levels and bone mineralization, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, also acts as a modulator of cell growth and differentiation in a number of cell types, including breast cancer cells. The anti-proliferative effects of 1,25(OH)(2)D(3) have been linked to suppression of growth stimulatory signals and potentiation of growth inhibitory signals, which lead to changes in cell cycle regulators such as p21(WAF-1/CIP1) and p27(kip1), cyclins and retinoblastoma protein as well as induction of apoptosis. Such studies have led to interest in the potential use of 1,25(OH)(2)D(3) in the treatment or prevention of certain cancers. Since this approach is limited by the tendency of 1,25(OH)(2)D(3) to cause hypercalcaemia, synthetic vitamin D analogues have been developed which display separation of the growth regulating effects from calcium mobilizing actions. This review examines mechanisms by which 1,25(OH)(2)D(3) and its active analogues exert both anti-proliferative and pro-apoptotic effects and describes some of the synthetic analogues that have been shown to be of particular interest in relation to breast cancer.

scholarly journals The Effect of the Combination of Vitamin K2 and Genistein, Coumestrol and Daidzein on the Osteoblast Differentiation and Bone Matrix Formation

2016 ◽  
Vol 10 (2) ◽  
pp. 12-19
Author(s):  
Sahar S. Karieb ◽  
Mohammed M. Jawad ◽  
Hanady S. Al-Shmgani ◽  
Zahraa H.M. Kadri
Keyword(s):  
Bone Formation ◽  
Osteoblast Differentiation ◽  
Nuclear Factor Kappa B ◽  
Type I Collagen ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Vitamin K2 ◽  
Type I ◽  
Nuclear Factor ◽  
Effective Factor

Multiple studies have been reported the stimulatory effect of the combinations of nutrients factors on bone formation. One such factor is vitamin K2 which can be associated with bone protective activities. The effect of vitamin K2 alone and in combination with genistein, coumestrol and daidzein on osteoblast differentiation and mineralization were tested. Significantly, vitamin K2 increased bone mineralization in combination with genistein (10-5M), coumestrol (10-7M) and daidzein (10-5M). However, there is no additive effect of this vitamin on alkaline phosphatase (ALP) levels in osteoblasts. By contrast, vitamin K2 enhanced the stimulatory effect of type I collagen and osteocalcin expression. Vitamin K2 alone increased RUNX and OSX expression while there is no synergistic effect with tested compound; this vitamin also did not modulate nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) ratio expression. These results suggested that vitamin K2 can be more effective factor in the presence of phytoestrogens on the improvement of bone formation after menopause.

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.

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.

scholarly journals Selective localization of a Golgi apparatus acid phosphatase isoenzyme in bone using pyridoxal-5'-phosphate.

1980 ◽  
Vol 28 (2) ◽  
pp. 115-123 ◽  
Author(s):  
R A Coleman ◽  
B H Schofield ◽  
D F McDonald
Keyword(s):  
Acid Phosphatase ◽  
Golgi Apparatus ◽  
Soft Tissues ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Thiamine Pyrophosphate ◽  
Selective Localization ◽  
Strong Staining ◽  
Matrix Components ◽  
Substrate Medium

Substrates commonly used for localizing bone Golgi apparatus (GA) acid phosphatase (AcPase), e.g., beta-glycerophosphate, p-nitrophenylphosphate, cytidine-5'-monophosphate, and di(dicyclohexylammonium)-2-napthylthiolphosphate, give strong staining not only of GA but also of lysosomes. Thiamine pyrophosphate and inosine-5'-monophosphate--substrates that give good GA staining in some soft tissues--give only lysosomal staining in bone. No previously used substrate or substrate-effector combination has selectively localized the GA acid phosphatase in bone. This article describes results using a new AcPase medium having pyridoxal-5'-phosphate (PLP) as substrate. In bone this medium produced strong staining of the osteoblast GA, but relatively little staining of lysosomes, including lysosomes in osteoclasts. The weak lysosomal staining was almost totally eliminated, without affecting the GA reaction, by pretreating the tissue in 0.3% NH3 solution. Conversely, elevated ionic strength of the substrate medium eliminated the GA reaction, while having little effect on lysosomal staining. The GA enzyme was very sensitive to 1 mM tartrate whereas the lysosomal enzyme was not. These differences suggest the presence of distinct isoenzymes in the two locations. The distribution of osteoblasts with stained GA coincided with the distribution of strongest alkaline phosphatase activity and rapid bone mineralization, supporting previous suggestions that osteoblast GA AcPase is involved in the processing of one or more newly synthesized bone matrix components.

ZINC, COPPER AND MANGANESE DEFICIENCIES AND THE RUMINANT SKELETON: A REVIEW

1980 ◽  
Vol 60 (3) ◽  
pp. 579-590 ◽  
Author(s):  
M. HIDIROGLOU
Keyword(s):  
Structural Integrity ◽  
Zinc Concentration ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Active Role ◽  
Deficient Diet ◽  
Prominent Symptom ◽  
Zinc Deficient Diet ◽  
Bone Abnormalities ◽  
Cattle And Sheep

This review deals with changes in the morphology and composition of the skeleton of ruminants caused by trace element deficiencies, specifically with respect to zinc, copper and manganese. When ruminants are fed a zinc-deficient diet, bone abnormalities occur. Zinc is also reported to be of value in the prevention or cure of footrot in cattle and sheep. Depletion of zinc reserves appears to lead to alterations in bone mineralization and reduction of bone zinc concentration. The bones of copper-deficient ruminants are fragile and easily broken. The most prominent symptom of this deficiency is a very marked stiffness of the legs. Copper-deficient animals show symptoms of rickets with beading of the ribs and enlargement of the ends of the long bones. Histologically, the affected bones show widening of the growth plate and the overall appearance of the lesion is that of osteoporosis. Crosslinking between collagen precursors is impaired in copper deficiency, which affects the structural integrity of collagen. There is no evidence of any correlation between the concentration of copper in bone and the severity of malformation. A relationship between low manganese intake by gestating ruminants and increased incidence of deformed calves or lambs has been demonstrated. The deformities observed included enlarged joints and twisted forelimbs. Histological examinations of the affected bones revealed retarded growth. Since manganese plays an active role in bone matrix formation, synthesis of mucopolysaccharide is reduced in the deficient bones. The synthesis of chondroitin sulfate, which is involved in maintaining the rigidity of connective tissue, is also affected during manganese deficiency, resulting in skeletal abnormalities.

scholarly journals Is the Vitamin D Receptor Found in Muscle?

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 354-363 ◽  
Author(s):  
Yongji Wang ◽  
Hector F. DeLuca
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Bone Mineralization ◽  
Active Form ◽  
Dihydroxyvitamin D3 ◽  
Neuromuscular Activity ◽  
Immunohistochemical Assay ◽  
Underlying Mechanisms ◽  
Positive Results ◽  
Phosphorus Levels

Abstract The active form of vitamin D, 1α,25-dihydroxyvitamin D3, is critical for the regulation of serum calcium and phosphorus levels that in turn support bone mineralization and neuromuscular activity. It is well known that vitamin D deficiency causes rachitic/osteomalacic myopathy and cardiac disorder and the provision of vitamin D can reverse the symptoms. However, the underlying mechanisms remain unclear. The question of whether the vitamin D receptor is found in muscle has been debated but not settled. We recently studied all available antibodies against the vitamin D receptor and found that most antibodies used detect proteins other than the vitamin D receptor, and therefore, the utility of these antibodies may generate the false-positive results. Using antibodies that do not detect proteins in tissues from vitamin D receptor null mice, we have developed a specific and sensitive immunohistochemical assay. The results from this investigation show that the vitamin D receptor is undetectable in skeletal, cardiac, and smooth muscle, suggesting that the function of vitamin D on muscle is either of an indirect nature or does not involve the known receptor.

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 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.

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