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PubMed2005

Architecture and mineralization of developing trabecular bone in the pig mandibular condyle.

Architecture and mineralization are important determinants of trabecular bone quality. To date, no quantitative information is available on changes in trabecular bone architecture and mineralization of newly formed bone during development. Three-dimensional architecture and mineralization of the trabecular bone in the mandibular condyle from six pigs of different developmental ages were investigated with micro-CT. Anteriorly in the condyle, a more advanced state of remodeling was observed than posteriorly, where more active growth takes place. Posteriorly, the bone volume fraction increased with age (r=0.87; P<0.05) by an increase of trabecular thickness (r=0.88; P<0.05), while the number of trabeculae declined (r=-0.86; P<0.05). Anteriorly, despite an increase in trabecular thickness (r=0.97; P<0.001), there was no change in bone volume fraction due to a simultaneous decline in trabecular number (r=-0.84; P<0.05) and increase in trabecular separation (r=0.95; P<0.01). Posteriorly, rods were remodeled into plates as expressed by the structure model index (r=-0.97; P<0.001), whereas anteriorly, a plate-like structure was already present in early stages. The trabecular structure had a clear orientation throughout the developmental process. The global degree of mineralization increased both anteriorly (r=0.86; P<0.05) and posteriorly (r=0.89; P<0.05). We suggest that the degree of mineralization does not depend on the bone volume, but on the thickness of the trabeculae as the mineralized centers of trabeculae were getting larger and more highly mineralized with age compared to their appositional layers. This indicates that besides apposition of new bone material on the surface of trabeculae, the mineralized tissue in their centers still changes and matures.

Animals↗
PubMed1976

Ultrastructural development of bone marrow adipose cell.

The postnatal development of bone marrow adipose cells was studied by sequential examination of marrow tissue obtained from the tibia and femur of 1- to 8-week-old rabbits. The bone marrow adipocyte begins to develop 2 weeks after birth. Its cellular origin differs from the "fibroblast-like" cell that is the progenitor of the extramedullary adipocyte. The marrow pre-adipocyte is associated with the sinus endothelium and adventitial cells, but is not associated with collagen and does not contain abundant organized rough endoplasmic reticulum. Unlike the extramedullary adipocyte, the course of differentiation of the medullary adipocyte is not characterized by the appearance of glycogen; furthermore, during the coalescence of lipid droplets to form larger fat globules, cytoplasmic organelles, such as mitochondria and ribosomes, are trapped within the lipid substance to form intralipid vacuoles containing degraded cytoplasmic organelles. The possible significance of these morphologic differences between the developing bone marrow adipocyte and that of its extramedullary counterpart is discussed.

Adipose Tissue↗
PubMed2003

RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through an ERK1/2-dependent mechanism.

Development of bone depends on a continuous supply of bone-degrading osteoclasts. Although several factors such as the matrix metalloproteinases and the integrins have been shown to be important for osteoclast recruitment, the mechanism of action remains poorly understood. In this study we investigated the molecular mechanisms homing osteoclasts to their future site of resorption during bone development. We show that RANKL and VEGF, two cytokines known to be present in bone, possess chemotactic properties toward osteoclasts cultured in modified Boyden chambers. Furthermore, in ex vivo cultures of embryonic murine metatarsals, a well established model of osteoclast recruitment, antagonists of RANKL and VEGF reduced calcium release, showing that both cytokines play roles during bone development. In cultures of purified osteoclasts both RANKL and VEGF induced phosphorylation of ERK1/2 MAP kinase. M-CSF, a well-known chemoattractant of osteoclast, also induced activation of ERK1/2, although this activation followed a kinetic pattern differing from that of RANKL and VEGF. RANKL and VEGF-induced, but not M-CSF-induced, osteoclast invasion was completely blocked by the specific inhibitor of ERK1/2 phosphorylation, PD98059. In addition, PD98059 was able to inhibit calcium release in cultures of embryonic metatarsals. In contrast, PD98059 was unable to abrogate the RANKL-induced calcium release in the tibia model, demonstrating that only some of the RANKL functions on osteoclast physiology are regulated through the ERK1/2 pathway. Taken together, these results show that RANKL and VEGF, in addition to their role in osteoclast differentiation and activation of resorption, are important components of the processes regulating osteoclast chemotaxis.

Animals↗
PubMed1989

Cartilage resorption and endochondral bone formation during the development of long bones in chick embryos.

Cartilage resorption during long bone development in the chick embryo varies in several crucial aspects from that in mammals. Cartilage does not calcify prior to resorption, the pattern of vascular tunnelling is not as regular as that in mammals and no distinct growth plate or secondary ossification centre is apparent. Primary cartilage resorption is preceded by diffusion of substances which produce a change in the cartilage matrix and necrosis of adjacent chondrocytes. Mononuclear phagocytes resorb the bulk of uncalcified cartilage, but resorption is slowed down by the formation of an osteoid band along the walls of the marrow tunnels. This prevents resorbing cells from gaining access to the cartilage matrix. If this osteoid band is in alignment with the trabecular structure, it may contribute to structural bone. In some areas chondrocytes transform into, or are replaced by, bone-producing cells and osteoid is observed within the chondrocyte lacunae. Some calcification of cartilage is observed after 16 days in ovo, but this is independent of cartilage resorption. Remnants of calcified cartilage frequently persist in the marrow cavity and multinucleated chondroclasts are required to resorb these remnants.

Acid Phosphatase↗
PubMed1999

Bone image segmentation.

Characteristics of microscopic structures in bone cross sections carry essential clues in age determination in forensic science and in the study of age-related bone developments and bone diseases. Analysis of bone cross sections represents a major area of research in bone biology. However, traditional approaches in bone biology have relied primarily on manual processes with very limited number of bone samples. As a consequence, it is difficult to reach reliable and consistent conclusions. In this paper we present an image processing system that uses microstructural and relational knowledge present in the bone cross section for bone image segmentation. This system automates the bone image analysis process and is able to produce reliable results based on quantitative measurements from a large number of bone images. As a result, using large databases of bone images to study the correlation between bone structural features and age-related bone developments becomes feasible.

Adolescent↗
PubMed1990

Adrenergic innervation of the calvarium of the neonatal rat. Its relationship to the sagittal suture and developing parietal bones.

The presence and distribution of adrenergic nerves in the developing calvarium of the newborn rat documented by means of the formaldehyde-induced fluorescence technique in rats aged 2 or 7 days. Nerve fibres exhibiting catecholamine-specific fluorescence were seen within the developing calvarium of all animals. In coronal sections, these fibres could be seen in the developing bone, especially in the lamina interna, while in sagittal sections, they were seen to traverse the tissue to reach the central of the diploë. These fibres originate from a denser plexus within the dura mater. Especially in the younger age group, the fluorescent fibres often exhibited an immature appearance, being coarse and devoid of varicosities. In the older animals the fibres were often varicose. The sutural tissue proper was always found to be devoid of adrenergic innervation. The possible origin and functional significance of the adrenergic innervation in the developing bone in relation to skull growth and sutural closure are discussed.

Adrenergic Fibers↗
PubMed2004

Lifestyle factors and the development of bone mass and bone strength in young women.

OBJECTIVE: To evaluate the contributions of adolescent calcium intake, oral contraceptive use, and exercise on bone mass and bone strength.Study design Eighty white women participated in 10 years of the Penn State Young Women's Health Study, a longitudinal study of community participants. We measured bone mineral mass (g), density (BMD, g/cm(2)), and body composition from dual energy x-ray absorptiometry and estimated proximal femur section modulus (bone bending strength). Calcium intake was determined from 45 days of prospective food records at regular intervals between the ages of 12 and 22 years. Exercise history and oral contraceptive use were assessed by questionnaire. RESULTS: Daily calcium intakes between the ages of 12 and 22 years ranged from 500 to 1900 mg/d and were not significantly associated with bone gain or bone strength. Oral contraceptive use during adolescence was not correlated with bone or body composition measurements. Femoral neck BMD did not change from 17 to 22 years of age, but section modulus increased 3% (P <.05). Only exercise during adolescence was significantly associated with increased BMD and bone bending strength. CONCLUSIONS: Adolescent lifestyle patterns can influence young adult bone strength. Our data suggest that exercise is the predominant lifestyle determinant of bone strength for this cohort.

Adolescent↗
PubMed1997

The assessment of development of bone mass in children by quantitative ultrasound through the proximal phalanxes of the hand.

The purpose of this study was to determine the relationship between quantitative ultrasound and age and body size, and to establish reference ranges for speed of sound (Ad-SoS) in the phalanxes of children. Healthy children (433), aged from 9 to 15 y were studied (226 girls and 207 boys). Ultrasound device (DBM Sonic 1200, IGEA, Italy) measuring the Ad-SoS through the phalanxes was used. Up to 11 y, the mean values for boys and girls were not significantly different. The increase of values was observed in the girls at 11 y, in the boys 2 y later. Stepwise multiple linear-regression analysis has shown that, in girls, the main factor influencing Ad-SoS was age and, in boys, height and weight. In the study, the ability of measurements of proximal phalanxes to reveal skeletal changes in healthy Polish children was shown. The study enabled us to establish the reference curves for healthy Polish children.

Adolescent↗
PubMed1998

Decreased bone mass and bone elasticity in mice lacking the transforming growth factor-beta1 gene.

Transforming growth factor-beta1 (TGF-beta1) knockout (TGF-beta1(-/-)) mice were used to investigate the role of TGF-beta1 in postnatal bone development. Volumetric bone mineral density (BMD) and mineral content (BMC) in these mice and in their normal (TGF-beta1(+/+)) and heterozygous (TGF-beta1(+/-)) littermates were analyzed by quantitative computed tomography (pQCT). Analysis of the proximal tibial metaphysis showed a significant decrease in the BMC of the TGF-beta1(-/-) mice compared to TGF-beta1(+/+) or TGF-beta1(+/-) mice; however, no significant difference was observed in BMD between the groups of mice. pQCT analysis of the tibial midshaft diaphysis showed no difference in the BMD or BMC of cortical bone between the groups. Histomorphometry revealed no significant difference in trabecular connectivity or in trabecular bone volume, number, or thickness. However, the width of the tibial growth plate and the longitudinal growth rate were significantly decreased in the TGF-beta1(-/-) mice, resulting in shorter tibia. Acoustic velocity measurements showed significant differences between the groups of mice with an apparent dosage effect of TGF-beta1 expression on the anisotropic properties of the bone. These data show that longitudinal growth and total mineral content are affected in mice lacking TGF-beta1, as well as the elastic properties of the bone, consistent with an important role for TGF-beta1 in bone modeling and bone quality.

Animals↗
PubMed1998

New developments in bone formation.

Two independent strategies have established that the transcription factor, Cbfa1, is a key regulator of both osteoblast differentiation and osteoblast-specific gene expression. Gene targeting experiments in mice have also shown that haploinsufficiency of Cbfa1 expression causes symptoms reminiscent of the Cleidocranial dysplasia syndrome (CCD), a heritable disorder of the skeleton. Direct analysis of the Cbfa1 gene in CCD families has revealed a direct correlation between mutations in this gene and disease phenotype.

Animals↗
PubMed2003

The development of bone mass and bone strength in the mandible of the female rat.

The present study provides baseline data for a number of mandibular growth dimensions, specially on bone mass and bone strength, that were collected between the 21st and the 180th days of postnatal life, which are intended as a reference for researchers designing experimental studies, specially on mandibular catch-up growth, and as an aid for clinicians who must evaluate results from published animal studies for validity and potential extrapolation to the human clinical situation. Fifty weanling female Wistar (Hsd:Wi) rats were fed ad libitum a diet previously shown to allow normal, undeformed mandibular growth. Five of them were randomly selected at different times between 21 and 180 d of life. Mandibular growth was estimated directly on the right hemimandible by taking measurements between anatomical points; mandibular bone mass (calcium mass) was estimated from the mg of calcium, determined by atomic absorption spectrophotometry, present in the ashes of the left hemimandible; and mechanical properties of the right hemimandible were determined using three-point bending mechanical test. Dimensions, bone calcium mass and bone strength of the female rat mandible increased linearly from day 21 to approximately day 90. Bone growth, as expected, was more than twice when assessed from bone weight than when derived from mandibular area, length or height when the parameters were expressed as the relative increase from the mean infant condition. The growth rate of the posterior part of the mandible (behind the third molar) was almost five times greater than that of the anterior part. The rates of growth of the studied parameters showed a marked decline after day 90. ANOVA indicated that no statistical differences were found between day 90 and day 120 values. It could be concluded that the female rat mandible attains its adult size, peak bone calcium mass and bone structural mechanical properties at some point between 90 and 120 d of postnatal life. Because of the extremely high positive correlation between mandibular bone calcium mass and both mandibular area and mandibular weight, it was possible to calculate the mandibular peak bone mass from the relations 7.69 mgCa/cm2 and 0.19 mgCa/mg bone.

Aging↗