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Title: Accretion of Bone Quantity and Quality in the Developing Mouse Skeleton

Abstract

To meet the mechanical challenges during early development, the skeleton requires the rapid accretion of bone quality and bone quantity. Here, we describe early bone development in the mouse skeleton and test the hypothesis that specific compositional properties determine the stiffness of the tissue. Tibias of female BALB mice were harvested at eight time-points (n = 4 each) distributed between 1 and 40 days of age and subjected to morphometric ({mu}CT), chemical (Fourier transform infrared microscpectroscopy), and mechanical (nanoindentation) analyses. Tibias of 450-day-old mice served as fully mineralized control specimens. In this work, we found that bone mineral formation proceeded very rapidly in mice by 1 day of age, where the degree of mineralization, the tissue mineral density, and the mineral crystallinity reached 36%, 51%, and 87% of the adult values, respectively. However, even though significant mineralization had occurred, the elastic modulus of 1-day-old bone was only 14% of its adult value, indicating that the intrinsic stiffening of the bone lags considerably behind the initial mineral formation.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
929967
Report Number(s):
BNL-80571-2008-JA
Journal ID: ISSN 0884-0431; JBMREJ; TRN: US200822%%947
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Bone and Mineral Research; Journal Volume: 22; Journal Issue: 7
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DENSITY; FEMALES; FLEXIBILITY; HYPOTHESIS; MICE; MINERALIZATION; MINERALS; SKELETON; national synchrotron light source

Citation Formats

Miller,L., Little, W., Schirmer, A., Sheik, F., Busa, B., and Judex, S. Accretion of Bone Quantity and Quality in the Developing Mouse Skeleton. United States: N. p., 2007. Web. doi:10.1359/jbmr.070402.
Miller,L., Little, W., Schirmer, A., Sheik, F., Busa, B., & Judex, S. Accretion of Bone Quantity and Quality in the Developing Mouse Skeleton. United States. doi:10.1359/jbmr.070402.
Miller,L., Little, W., Schirmer, A., Sheik, F., Busa, B., and Judex, S. Mon . "Accretion of Bone Quantity and Quality in the Developing Mouse Skeleton". United States. doi:10.1359/jbmr.070402.
@article{osti_929967,
title = {Accretion of Bone Quantity and Quality in the Developing Mouse Skeleton},
author = {Miller,L. and Little, W. and Schirmer, A. and Sheik, F. and Busa, B. and Judex, S.},
abstractNote = {To meet the mechanical challenges during early development, the skeleton requires the rapid accretion of bone quality and bone quantity. Here, we describe early bone development in the mouse skeleton and test the hypothesis that specific compositional properties determine the stiffness of the tissue. Tibias of female BALB mice were harvested at eight time-points (n = 4 each) distributed between 1 and 40 days of age and subjected to morphometric ({mu}CT), chemical (Fourier transform infrared microscpectroscopy), and mechanical (nanoindentation) analyses. Tibias of 450-day-old mice served as fully mineralized control specimens. In this work, we found that bone mineral formation proceeded very rapidly in mice by 1 day of age, where the degree of mineralization, the tissue mineral density, and the mineral crystallinity reached 36%, 51%, and 87% of the adult values, respectively. However, even though significant mineralization had occurred, the elastic modulus of 1-day-old bone was only 14% of its adult value, indicating that the intrinsic stiffening of the bone lags considerably behind the initial mineral formation.},
doi = {10.1359/jbmr.070402},
journal = {Journal of Bone and Mineral Research},
number = 7,
volume = 22,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
  • Short durations of extremely small magnitude, high-frequency, mechanical stimuli can promote anabolic activity in the adult skeleton. Here, it is determined if such signals can influence trabecular and cortical formative and resorptive activity in the growing skeleton, if the newly formed bone is of high quality, and if the insertion of rest periods during the loading phase would enhance the efficacy of the mechanical regimen. Eight-week-old female BALB/cByJ mice were divided into four groups, baseline control (n = 8), age-matched control (n = 10), whole-body vibration (WBV) at 45 Hz (0.3 g) for 15 min day{sup -1} (n = 10),more » and WBV that were interrupted every second by 10 of rest (WBV-R, n = 10). In vivo strain gaging of two additional mice indicated that the mechanical signal induced strain oscillations of approximately 10 microstrain on the periosteal surface of the proximal tibia. After 3 weeks of WBV, applied for 15 min each day, osteoclastic activity in the trabecular metaphysis and epiphysis of the tibia was 33% and 31% lower (P < 0.05) than in age-matched controls. Bone formation rates (BFR{center_dot}BS{sup -1}) on the endocortical surface of the metaphysis were 30% greater (P < 0.05) in WBV than in age-matched control mice but trabecular and middiaphyseal BFR were not significantly altered. The insertion of rest periods (WBV-R) failed to potentiate the cellular effects. Three weeks of either WBV or WBV-R did not negatively influence body mass, bone length, or chemical bone matrix properties of the tibia. These data indicate that in the growing skeleton, short daily periods of extremely small, high-frequency mechanical signals can inhibit trabecular bone resorption, site specifically attenuate the declining levels of bone formation, and maintain a high level of matrix quality. If WBV prove to be efficacious in the growing human skeleton, they may be able to provide the basis for a non-pharmacological and safe means to increase peak bone mass and, ultimately, reduce the incidence of osteoporosis or stress fractures later in life.« less
  • The administration of stable Ca or Sr to decrease the retention of radiostrontium by skeletal tissue has been employed by a number of investigators with equivocal results. The experiments were based chiefly on the carrier effect, the dilution of radiostrontiuru with stable Sr or Ca adruinistered just prior to or immediately after the adrninistration of the radiostrontium. A different approach was used to decrease the Sr/sup 85/ retention. This procedure is based on the hypothesis that a monolayer of Sr salts will be bound to the reactive sites of binding on the surface of the inoramic bone crystal with greatermore » force than will a subsequent layer of Sr salts, since Ca phosphate is less soluble than Sr phosphate. Accordingly, stable Sr was administered in the diet for periods ranging from 2 to 7 days prior to the injection of Sr/sup 85/. Similar use of stable Ca and Zr was also investigated. It was found that there was a decrease of 76% in the retention of Sr/sup 85/ in young growing rats receiving a high-Sr diet for 7 days, as compared with animals fed a stock diet. The decreased uptake of Sr/sup 85/ was reflected in a decrease of both the Sr exchange capacity and the Sr accretion rate of the skeleton. A high-Ca diet also produced a decrease in the Sr/sup 85/, but much less than a Sr diet, and a Zr sulfate-supplemented stock diet was a little more effective than the high-Ca diet. (auth)« less
  • The mammalian erythrocyte membrane skeleton primarily consists of spectrin, actin, protein 4.1 (numerals refer to electrophoretic mobility on SDS-PAGE gels), and dematin (protein 4.9). Although the functional interactions of spectrin, actin, and protein 4.1 have been extensively characterized, virtually nothing is known about the physiological role of dematin. Spectrin is present as elongated heterodimers of {alpha}- and {beta}-subunits arranged in a two-dimensional array just beneath the plasma membrane. The mechanism by which the {open_quotes}head{close_quotes} region of the spectrin dimer binds to the plasma membrane via ankyrin and band 3 is well established. However, the mechanism by which the {open_quotes}tail{close_quotes} endmore » of spectrin is anchored to the plasma membrane is not completely understood. The region containing the spectrin tails is called the junctional complex. Protein 4.1, actin, adducin, and dematin have been directly visualized as components of junctional complexes. Other components of junctional complexes include tropomyosin, tropomodulin, and p55. Protein 4.1 acts as an adaptor protein, linking spectrin-actin complexes to the plasma membrane. Dematin binds actin and therefore also may function as an adaptor protein in mature erythrocytes. Dematin also displays phosphorylation-dependent actin bundling activity. Since actin bundles appear to be absent from mature erythrocytes, this property may be most relevant during erythropoiesis and in nonerythroid cells. The cDNA sequence of human dematin shows significant identity with the {open_quotes}headpiece{close_quotes} of villin, an actin bundling protein of brush border cytoskeleton. Unlike villin, dematin is a widely distributed protein and may substitute for villin to regulate actin bundling events by a phosphorylation-dependent mechanism. 18 refs., 1 fig.« less
  • The main object of this study was to provide quantitative information on the distribution and retention of /sup 32/P, /sup 45/Ca, /sup 85/ Sr, and /sup 133/Ba in the mouse skeleton as a function of age at the time of injection. At 24 hr after intraperitoneal (i.p.) injection into 8-week old mice, the distribution of four radionuclides throughout the skeleton was essentially identical. In the case of /sup 85/Sr, however, the skeleton accumulated about 90% of the total body activity at this time, whereas for /sup 32/P the amount was only about 40%. The levels of accumulation of activity bymore » the bones depended upon the age of the animals at the time of injection. Thus at 24 hr after i.p. injection of /sup 85/Sr into 3 and 26-week old animals the concentration of /sup 85/Sr in the bones varied by factors of less than 1.5 and 5 respectively. These differences were attributed mainly to the degree of vascularization and the surface area available for absorption in individual bones. The relative concentrations of activity in the bones changed considerably with time after injection due mainly to varying rates of loss of activity from different bones. In older animals the levels of activity in the various bones became more uniform with time but in the youngest mice injected (3 weeks old) concentrations in individual bones varied by about a factor of 9 by l28 days after injection. It was also shown that in the mouse there is no significant release of /sup 90/Y formed from /sup 90/Sr deposited in bone. (auth)« less