scholarly journals Pancreas deficiency modifies bone development in the ovine fetus near term

2021 ◽  
Author(s):  
Stuart A Lanham ◽  
Dominique Blache ◽  
Richard Oc Oreffo ◽  
Abigail L Fowden ◽  
Alison J Forhead

Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-computed tomography and an electromagnetic 3-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomised fetuses compared to control fetuses, limb lengths were shorter and trabecular bone in the metatarsi showed greater bone volume fraction, trabecular thickness, degree of anisotropy and porosity, and lower fractional bone surface area and trabecular spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth.

2021 ◽  
Author(s):  
Ursula Föger-Samwald ◽  
Maria Papageorgiou ◽  
Katharina Wahl-Figlash ◽  
Katharina Kerschan-Schindl ◽  
Peter Pietschmann

AbstractMuscle force is thought to be one of the main determinants of bone development. Hence, peak muscle growth is expected to precede peak bone growth. In this study, we investigated muscle and bone development in female C57BL/6 J, DBA/2JRj, and C3H/HeOuJ mice. Femoral cortical and trabecular bone structure and the weights of selected muscles were assessed at the ages of 8, 16, and 24 weeks. Muscle mass increased from 8 to 24 weeks in all 3 strains, suggesting peak muscle development at 24 weeks or later. Bone volume fraction, trabecular number, and connectivity density of the femur decreased or remained unchanged, whereas trabecular density and trabecular thickness largely increased. These results suggest a peak in trabecular bone accrual at 8 weeks or earlier followed by further increases in density and structural reorganization of trabeculae. Cortical density, cortical thickness, and cortical cross sectional area increased over time, suggesting a peak in cortical bone accrual at 24 weeks or later. In conclusion, our data provide evidence that growth of muscle lags behind trabecular bone accrual.


2011 ◽  
Vol 209 (1) ◽  
pp. 21-32 ◽  
Author(s):  
William F Powell ◽  
Kevin J Barry ◽  
Irena Tulum ◽  
Tatsuya Kobayashi ◽  
Stephen E Harris ◽  
...  

Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous, and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10 kb-Dmp1 promoter drives a tamoxifen-inducible Cre-recombinase were mated with animals in which exon 1 of PPR is flanked by lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPRcKO mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPRcKO mice. Reduction of trabeculae number and thickness was also detected by micro-computed tomography analysis whereas bone volume fraction (BV/TV%) was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPRcKO mice were subjected to a low-calcium diet to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPRcKO animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis.


2003 ◽  
Vol 82 (10) ◽  
pp. 819-823 ◽  
Author(s):  
L.J. van Ruijven ◽  
E.B.W. Giesen ◽  
M. Farella ◽  
T.M.G.J. van Eijden

The mechanical properties of cancellous bone depend on the bone structure. The present study examined the extent to which the apparent stiffness of the cancellous bone of the human mandibular condyle can be predicted from its structure. Two models were compared. The first, a structure model, used structural parameters such as bone volume fraction and anisotropy to estimate the apparent stiffness. The second was a finite element model (FEM) of the cancellous bone. The bone structure was characterized by micro-computed tomography. The calculated stiffnesses of 24 bone samples were compared with measured stiffnesses. Both models could predict 89% of the variation in the measured stiffnesses. From the stiffness approximated by FEM in combination with the measured stiffness, the stiffness of the bone tissue was estimated to be 11.1 ± 3.2 GPa. It was concluded that both models could predict the stiffness of cancellous bone with adequate accuracy.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1562 ◽  
Author(s):  
Kaori Endo ◽  
Satoshi Yamada ◽  
Masahiro Todoh ◽  
Masahiko Takahata ◽  
Norimasa Iwasaki ◽  
...  

The incidence of osteoporotic fractures was estimated as nine million worldwide in 2000, with particular occurrence at the proximity of joints rich in cancellous bone. Although most of these fractures spontaneously heal, some fractures progressively collapse during the early post-fracture period. Prediction of bone fragility during progressive collapse following initial fracture is clinically important. However, the mechanism of collapse, especially the gradual loss of the height in the cancellous bone region, is not clearly proved. The strength of cancellous bone after yield stress is difficult to predict since structural and mechanical strength cannot be determineda priori. The purpose of this study was to identify whether the baseline structure and volume of cancellous bone contributed to the change in cancellous bone strength under cyclic loading. A total of fifteen cubic cancellous bone specimens were obtained from two 2-year-old bovines and divided into three groups by collection regions: femoral head, neck, and proximal metaphysis. Structural indices of each 5-mm cubic specimen were determined using micro-computed tomography. Specimens were then subjected to five cycles of uniaxial compressive loading at 0.05 mm/min with initial 20 N loading, 0.3 mm displacement, and then unloading to 0.2 mm with 0.1 mm displacement for five successive cycles. Elastic modulus and yield stress of cancellous bone decreased exponentially during five loading cycles. The decrease ratio of yield stress from baseline to fifth cycle was strongly correlated with bone volume fraction (BV/TV,r= 0.96,p< 0.01) and structural model index (SMI,r= − 0.81,p< 0.01). The decrease ratio of elastic modulus from baseline to fifth cycle was also correlated with BV/TV (r= 0.80,p< 0.01) and SMI (r= − 0.78,p< 0.01). These data indicate that structural deterioration of cancellous bone is associated with bone strength after yield stress. This study suggests that baseline cancellous bone structure estimated from adjacent non-fractured bone contributes to the cancellous bone strength during collapse.


1986 ◽  
Vol 110 (2) ◽  
pp. 225-231 ◽  
Author(s):  
A. L. Fowden ◽  
X. Z. Mao ◽  
R. S. Comline

ABSTRACT The effects of fetal pancreatectomy on the growth and metabolism of the fetal sheep were investigated in chronically catheterized animals during the last third of gestation. Fetal pancreatectomy reduced body weight and crown–rump length at delivery near term (term 145 days). Body weight was affected more than body length so the ratio of weight to length was significantly less after pancreatectomy than in intact animals (P < 0·05). Pancreatectomized fetuses appeared to maintain a normal growth rate for 5–10 days after surgery but thereafter showed no further significant increase in body weight. When all the data from the intact and pancreatectomized fetuses were combined, there was a significant positive correlation between the plasma insulin concentration in utero and the body weight at delivery near term. The majority of organs studied were reduced in absolute weight after pancreatectomy but only the spleen and thymus were proportionally lighter when the weights were expressed as a percentage of body weight. Brain and placental weights were similar in intact and pancreatectomized fetuses. Over the range of values observed in utero, there were significant inverse correlations between the log plasma insulin level and the mean plasma concentrations of glucose, lactate, fructose and α-amino-nitrogen in individual intact and pancreatectomized fetuses. Insulin infusion into pancreatectomized fetuses restored the metabolite concentrations to their normal values within 48 h of infusion. The results demonstrate that insulin has a vital role in regulating fetal growth and metabolism in utero. J. Endocr. (1986) 110, 225–231


2014 ◽  
Vol 5 (2) ◽  
pp. 53-58 ◽  
Author(s):  
S. den Dunnen ◽  
G. J. M. Tuijthof

Abstract. Using water jets in orthopedic surgery to drill holes in bones can be beneficial due to the absence of thermal damage and the always sharp cut. To minimize operating time and the volume of water that is used, the efficiency (volume of removed bone per added volume of water) of the water jet should be maximized. The goal was to study the effect of the open trabecular bone structure on the efficiency for different water jet diameters. 86 holes were drilled in porcine tali and femora submerged in water with nozzles of 0.3, 0.4, 0.5 and 0.6 mm at 70 MPa during 5 s and a standoff distance of 8 mm. MicroCT scans were made to measure the removed bone volume and the bone structural properties Trabecular Spacing (Tb.Sp.), Trabecular Thickness (Tb.Sp.) and Bone Volume Fraction (BV/TV). Pearson's correlation tests (p < 0.05, 95% confidence interval) were performed for each water jet diameter using the bone structural property as an independent factor and the efficiency as a dependent factor. No significant differences were found between the nozzle diameters in the material removal rates per added volume of water. The efficiency decreased for an increase in Tb.Th. and BV/TV for nozzles of 0.3, 0.4 and 0.5 mm. The 0.6 mm nozzle showed less influence of the Tb.Th. and BV/TV. The Tb.Sp. has no influence on the efficiency of a water jet. The total volume of added water combined with the Tb.Th. or BV/TV is a leading measure for the volume of bone material that is removed, which provides freedom in the development of water jet instruments as the nozzle diameter, pressure and jet time can be chosen in accordance to the maximum operating time requirements or dimensional limitations of a design.


2020 ◽  
Author(s):  
Bo Liu ◽  
Chen-Chen Ji ◽  
Yi-Jie Shao ◽  
Ting Liang ◽  
Jia-Heng He ◽  
...  

Abstract BackgroundEtoricoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor, is commonly used in osteoarthritis (OA) for pain relief. The purpose of our study was to investigate the effects of Etoricoxib on mouse subchondral bone in early OA.MethodsOA was induced via destabilization of the medial meniscus (DMM) in C57BL/6J mice. After surgery, the mice were randomly and equally divided into five groups: a sham-operated control group (Sham group), an osteoarthritis (OA) group (DMM group), an OA treated with Etoricoxib 5mg/kg (DMM+E5) group, an OA treated with Etoricoxib 10mg/kg (DMM+E10) group, and an OA treated with Etoricoxib 20mg/kg (DMM+E20) group. Mice in the Sham group and DMM group were injected with a similar dose of vehicle (40% ethyl alcohol–saline solution). Four weeks after treatment, mice were euthanized. Micro computed tomography (Mirco-CT) analysis, Safranin O-Fast Green staining, hematoxylin and eosin (HE) staining were performed to evaluate morphological and structural changes. In addition, atomic force microscopy (AFM) analysis was performed to evaluate changes in the elastic modulus. Furthermore, changes in microstructure were detected by scanning electron microscopy (SEM).ResultsEtoricoxib inhibited osteophyte formation in the subchondral bone. However, it also reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th), and more microfractures and pores were observed in the subchondral bone. Moreover, Etoricoxib reduced the elastic modulus of subchondral bone. Furthermore, exposure to Etoricoxib further increased the empty/total osteocyte ratio of the subchondral bone. In cartilage and synovium, Etoricoxib did not significantly change the Osteoarthritis Research Society International (OARSI) score, the modified Mankin score, and the synovialitis-score versus the DMM group. ConclusionOur results demonstrate that although Etoricoxib can relieve the pain induced by OA, it also has adverse effects on subchondral bone in early OA.


1995 ◽  
Vol 7 (3) ◽  
pp. 399 ◽  
Author(s):  
KT Ball ◽  
M Takeuchi ◽  
Y Yoneyama ◽  
GG Power

Because maximal nonshivering thermogenesis can commence only after occlusion of the umbilical cord, circulating stimulators and inhibitors were hypothesized to alter brown fat activity in the perinatal period. The roles of prostaglandin I2 (PGI2) and PGE2 in the initiation of nonshivering thermogenesis at birth were investigated. Indomethacin (45 mg bolus, 3 mg h-1 thereafter) was infused into 10 near-term fetal sheep to decrease prostanoid synthesis; 6 age-matched fetuses were infused with saline as controls. Sixteen hours later, birth was simulated in utero by sequentially cooling the fetus, ventilating its lungs with oxygen and occluding the umbilical cord. In the control fetuses, the plasma concentrations of PGI2 and PGE2 and free fatty acids, an index of nonshivering thermogenesis, were unaffected by cooling. Ventilation caused the concentration of PGI2 to increase 108% (P < 0.001) and that of PGE2 to decrease 26% (P < 0.05), while fatty acid concentrations increased 100% (P < 0.05). After cord occlusion, PGI2 concentrations remained elevated whereas PGE2 concentrations decreased a further 46% (P < 0.01), and fatty acid concentrations increased a further 100% (P < 0.05). In the indomethacin-treated fetuses, PGI2 and PGE2 concentrations decreased to 20% of the preinfusion values (P < 0.001) and did not change during the experiment. Cooling initiated a 300% increase in fatty acid concentrations (P < 0.05) and ventilation and cord occlusion induced no further significant changes. Thus, prostanoid concentrations follow changes in nonshivering thermogenic activity and support a regulatory role for PGI2 and PGE2 in the initiation of thermogenesis. Before birth, high concentrations of PGE2 favour suppression of thermogenesis, and after birth this inhibition is removed and there is stimulation by PGI2.


2018 ◽  
Vol 55 (6) ◽  
pp. 798-806 ◽  
Author(s):  
Nan Ru ◽  
Sean Shih-Yao Liu ◽  
Yuxing Bai ◽  
Song Li ◽  
Yunfeng Liu ◽  
...  

Objective: BoneCeramic can regenerate bone in alveolar defects, but it remains unknown whether it is feasible to move a tooth through BoneCeramic grafting sites. The objective of this study was to investigate three-dimensional real-time bone responses and micromechanical properties in the grafting sites during orthodontic tooth movement. Methods: Sixty 5-week-old rats were randomly assigned into three groups to receive BoneCeramic, natural bovine cancellous bone particles (Bio-Oss), and no graft, respectively, after the extraction of the left maxillary first molar. After 4 weeks, the maxillary left second molar was moved into the extraction for 28 days. Dynamic bone microstructures and root resorption were evaluated using in vivo micro-computed tomography and histology. Stress distribution of tooth roots and biomechanical properties of corresponding bone tissue were examined by finite element methods and nanoindentation. Mixed-model analysis of variance was performed to compare the difference among time points with Bonferroni post hoc tests at the significance level of P < .05. Results: The BoneCeramic group had the least amount of tooth movement and root resorption volume and craters, highest bone volume fraction, trabecular number, mean trabecular thickness, microhardness, and elastic modulus, followed by Bio-Oss and the control group. The highest stress accumulated in the cervical region of the mesial roots. Conclusion: BoneCeramic has better osteoconductive potential and biomechanical properties and induces less root resorption compared with Bio-Oss grafting and naturally recovered extraction site.


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