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.

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 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

The Influence of Age and Gender on Mandibular Indices among the Libyan Population

2019 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Negative Correlation ◽  
Bone Mineralization ◽  
Age Groups ◽  
T Test ◽  
Chi Square ◽  
Age And Gender ◽  
Significant Difference ◽  
Chi Square Test ◽  
And Gender ◽  
Libyan Population

Radiographic Mandibular Indices serve as easy and relatively cheap tools for evaluating bone mineralization. Objectives: To examine the effect of age and gender on three mandibular indices: the panoramic mandibular index (PMI), the mandibular ratio (MR) and the mandibular cortical index (MCI), among Libyan population. Methods: The three indices were measured on 317 digital (OPGs) of adult humans (155 males, 162 females). The sample was divided into six age groups (from 18-25 years through 56-65 years). The measurements were analyzed for interactions with age and sex, using SPSS (Statistical Package for Social Studies) software version no. 22. The tests employed were two way ANOVA, the unpaired T-test and chi-square test. Results: The mean PMI fluctuated between 0.37 s.d. 0.012 and 0.38 s.d. 0.012. among the sixth age groups. One-way ANOVA statistical test revealed no significant of age on PMI. On the other hand gender variation has effect on PMI, since independent sample t-test disclosed that the difference between the male and female PMI means statistically significant. ANOVA test showed that the means of MR among age groups showed a negative correlation i.e. MR mean declined from 3.01 in 18-25 age groups to 2.7 in 55-65 age groups. In contrary, the gender showed no effect on MR according two sample t-test at p> 0.05. In regards with MCI, statistical analysis showed that it affected by age that is C1 was decreasing by age while C2 and C3 were increased by age. Using chi square test the result indicated that there is a significant difference among the different age group and the two genders in MCI readings. Conclusion: PMI was influenced significantly by age but minimally by the gender. MR is not affected by gender but has a negative correlation with age. MCI is affected by both age and gender

scholarly journals Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption

1993 ◽  
Vol 268 (13) ◽  
pp. 9901-9907
Author(s):  
F.P. Ross ◽  
J. Chappel ◽  
J.I. Alvarez ◽  
D. Sander ◽  
W.T. Butler ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Matrix ◽  
Bone Sialoprotein ◽  
Matrix Proteins ◽  
Bone Matrix Proteins ◽  
Alpha V Beta 3

scholarly journals Effect of protein restriction on the messenger RNA contents of bone-matrix proteins, insulin-like growth factors and insulin-like growth factor binding proteins in femur of ovariectomized rats

1996 ◽  
Vol 75 (6) ◽  
pp. 811-823 ◽  
Author(s):  
Yusuke Higashi ◽  
Asako Takenaka ◽  
Shin-Ichiro Takahashi ◽  
Tadashi Noguchi
Keyword(s):  
Dietary Protein ◽  
Type I Collagen ◽  
Control Diet ◽  
Bone Matrix ◽  
Protein Restriction ◽  
Matrix Proteins ◽  
Type I ◽  
Bone Matrix Proteins ◽  
Mrna Content ◽  
Insulin Like Growth Factors

It has been reported that loss of ovarian oestrogen after menopause or by ovariectomy causes osteoporosis. In order to elucidate the effect of dietary protein restriction on bone metabolism after ovariectomy, we fed ovariectomized young female rats on a casein-based diet (50g/kg diet (protein restriction) or 200g/kg diet (control)) for 3 weeks and measured mRNA contents of bone-matrix proteins such as osteocalcin, osteopontin and α1 type I collagen, insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in femur. Ovariectomy decreased the weight of fat-free dry bone and increased urinary excretion of pyridinium cross-links significantly, although dietary protein restriction did not affect them. Neither ovariectomy nor protein restriction affected the content of mRNA of osteopontin and osteocalcin; however, ovariectomy increased and protein restriction extensively decreased the α1 type I collagen mRNA content in bone tissues. Ovariectomy increased IGF-I mRNA only in the rats fed on the control diet. Conversely, protein rest riction increased and ovariectomy decreased the IGF-II mRNA content in femur. Furthermore, the contents of IGFBP-2, IGFBP-4 and IGFBP-5 mRNA increased, but the content of IGFBP-3 mRNA decreased in femur of the rats fed on the protein-restricted diet. In particular, ovariectomy decreased the IGFBP-2 mRNA content in the protein-restricted rats and the IGFBP-6 mRNA content in the rats fed on the control diet. These results clearly show that the mRNA for some of the proteins which have been shown to be involved in bone formation are regulated by both quantity of dietary proteins and ovarian hormones.

Diet-related changes in mechanical properties of rat vertebrae

1992 ◽  
Vol 262 (2) ◽  
pp. R318-R321 ◽  
Author(s):  
G. J. Salem ◽  
R. F. Zernicke ◽  
R. J. Barnard
Keyword(s):  
Mechanical Properties ◽  
Vertebral Body ◽  
Calcium Metabolism ◽  
Bone Mineralization ◽  
Maximum Load ◽  
Control Group ◽  
Buffer Solution ◽  
Cross Sectional ◽  
Lumbar Vertebral Body ◽  
Significant Difference

High fat and sucrose (HFS) diets may induce glucose intolerance, alter calcium metabolism, and lead to deficits in bone mineralization, development, and mechanical properties. To determine the mechanical and structural consequences of a HFS diet on rapidly growing vertebrae, female Sprague-Dawley rats (8 wk) were assigned randomly (2:1) either to a control group (n = 20) fed a low-fat complex-carbohydrate diet or an experimental group (n = 10) fed a HFS diet for 10-12 wk. The sixth lumbar vertebral body (L6) was isolated from the pedicles, morphological measures were taken, and compression was tested at a fast strain rate, while immersed in a warmed (37 degrees C) isotonic physiological buffer solution. No significant difference in body mass existed between HFS and control groups; nevertheless, HFS L6 cross-sectional areas, lengths, and volumes were significantly smaller than controls. The HFS L6 also had significantly lower mechanical properties, including initial maximum load, energy at initial maximum load, and strain energy density at initial maximum load. Diets high in sucrose and fat content have been associated with changes in calcium metabolism, and the results of the current study suggest that in immature vertebrae, a HFS diet may adversely affect vertebral body mechanical integrity and strength.

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