scholarly journals The impact of bipedal mechanical loading history on longitudinal long bone growth

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0211692
Author(s):  
Adam D. Foster
1998 ◽  
Vol 157 (2) ◽  
pp. 225-235 ◽  
Author(s):  
H Robson ◽  
E Anderson ◽  
OB Eden ◽  
O Isaksson ◽  
S Shalet

Short stature is one of the most well recorded long term sequelae for adult survivors of childhood malignancies. It has become increasingly apparent that cytotoxic chemotherapy, as well as craniospinal irradiation, has a major impact on growth, but there are virtually no studies which explore the mechanisms by which these cytotoxic drugs affect growth. We have used an in vitro system to investigate the direct effects of a range of chemotherapeutic agents on the proliferative responses of rat tibial growth plate chondrocytes, both in suspension and monolayer culture. The glucocorticoids and purine anti-metabolites reduced chondrocyte proliferation both in monolayer and suspension cultures and this resulted from an increase in cell doubling times with a concomittant reduction in the numbers of S phase cells. DNA damaging agents (e.g. actinomycin-D) were also able to reduce chondrocyte proliferation, both in monolayer and suspension culture. This, however, was the result of a cell cycle arrest and subsequent cell death. In our studies, methotrexate had no significant effect on the proliferative responses of the chondrocytes either in monolayer or suspension culture. These results indicate direct effects of a range of chemotherapeutic agents on the proliferative responses of growth plate chondrocytes. Both cytostatic and cytotoxic effects were observed although the impact of either the potential loss of cells from the proliferative pool during chondrocyte differentiation, or the reduction in the rate of chondrocyte turnover on long bone growth remains to be elucidated.


Biology ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 12
Author(s):  
David Chavarri-Prado ◽  
Aritza Brizuela-Velasco ◽  
Ángel Álvarez-Arenal ◽  
Markel Dieguez-Pereira ◽  
Esteban Pérez-Pevida ◽  
...  

Objectives: To determine the effect of mechanical loading of bone on the stability and histomorphometric variables of the osseointegration of dental implants using an experimental test in an animal model. Materials and Methods: A total of 4 human implants were placed in both tibiae of 10 New Zealand rabbits (n = 40). A 6-week osseointegration was considered, and the rabbits were randomly assigned to two groups: Group A (Test group) included 5 rabbits that ran on a treadmill for 20 min daily during the osseointegration period; Group B (Controls) included the other 5 that were housed conventionally. The monitored variables were related to the primary and secondary stability of the dental implants (implant stability quotient—ISQ), vertical bone growth, bone to implant contact (BIC), area of regenerated bone and the percentage of immature matrix. Results: The results of the study show a greater vertical bone growth (Group A 1.26 ± 0.48 mm, Group B 0.32 ± 0.47 mm, p < 0.001), higher ISQ values (Group A 11.25 ± 6.10 ISQ, 15.73%; Group B 5.80 ± 5.97 ISQ, 7.99%, p = 0.006) and a higher BIC (Group A 19.37%, Group B 23.60%, p = 0.0058) for implants in the test group, with statistically significant differences. A higher percentage of immature bone matrix was observed for implants in the control group (20.68 ± 9.53) than those in the test group (15.38 ± 8.84) (p = 0.108). A larger area of regenerated bone was also observed for the test implants (Group A 280.50 ± 125.40 mm2, Group B 228.00 ± 141.40 mm2), but it was not statistically significant (p = 0.121). Conclusions: The mechanical loading of bone improves the stability and the histomorphometric variables of the osseointegration of dental implants.


1991 ◽  
Vol 124 (5) ◽  
pp. 602-607 ◽  
Author(s):  
Ben A. A. Scheven ◽  
Nicola J. Hamilton

Abstract. Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.


2019 ◽  
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  

AbstractLongitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation on EO.Rats given SR11237 from post-natal day 5 to 15 were harvested for micro-computed tomography scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole mount evaluation.RXR agonist-treated rats were smaller than controls, and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape corresponding with P57 immunostaining. Additionally, SOX9 positive cells were found surrounding the calcified tissue. The epiphysis of SR11237 treated bones showed increased TRAP staining, and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of treated animals. Isolated mouse long bones treated with SR11237 grew significantly less than their DMSO controls.This study demonstrates that stimulation of the RXR receptor causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models.


Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 736-744 ◽  
Author(s):  
Steven W. Lane ◽  
Serena De Vita ◽  
Kylie A. Alexander ◽  
Ruchan Karaman ◽  
Michael D. Milsom ◽  
...  

Abstract Hematopoietic stem cells (HSCs) interact with osteoblastic, stromal, and vascular components of the BM hematopoietic microenvironment (HM) that are required for the maintenance of long-term self-renewal in vivo. Osteoblasts have been reported to be a critical cell type making up the HSC niche in vivo. Rac1 GTPase has been implicated in adhesion, spreading, and differentiation of osteoblast cell lines and is critical for HSC engraftment and retention. Recent data suggest a differential role of GTPases in endosteal/osteoblastic versus perivascular niche function. However, whether Rac signaling pathways are also necessary in the cell-extrinsic control of HSC function within the HM has not been examined. In the present study, genetic and inducible models of Rac deletion were used to demonstrate that Rac depletion causes impaired proliferation and induction of apoptosis in the OP9 cell line and in primary BM stromal cells. Deletion of Rac proteins caused reduced trabecular and cortical long bone growth in vivo. Surprisingly, HSC function and maintenance of hematopoiesis in vivo was preserved despite these substantial cell-extrinsic changes. These data have implications for therapeutic strategies to target Rac signaling in HSC mobilization and in the treatment of leukemia and provide clarification to our evolving concepts of HSC-HM interactions.


Author(s):  
Jordan V. Inacio ◽  
DanielleM Cristino ◽  
Michael W. Hast ◽  
Hannah Dailey

Abstract Biomechanical testing of long bones can be subject to undesirable errors and uncertainty due to malalignment of specimens with respect to the mechanical axis of the test frame. To solve this problem, we designed a novel, customizable alignment and potting fixture for long bone testing. The fixture consisted of 3D-printed components modeled from specimen-specific CT scans to achieve a predetermined specimen alignment. We demonstrated the functionality of this fixture by comparing benchtop torsional test results to specimen-matched finite element models and found a strong and statistically significant correlation (R2 = 0.9536, p &lt; 0.001). Additional computational models estimated the impact of malalignment on mechanical behavior in both torsion and axial compression. Results confirmed that torsion testing is relatively robust to alignment artifacts, with absolute percent errors less than 8% in all malalignment scenarios. In contrast, axial testing was highly sensitive to setup errors, experiencing absolute percent errors up to 40% with off-center malalignment and up to 130% with angular malalignment. This suggests that whenever appropriate, torsion tests should be used preferentially as a summary mechanical measure. When more challenging modes of loading are required, pre-test clinical-resolution CT scanning can be effectively used to create potting fixtures that allow for precise pre-planned specimen alignment. This may be particularly important for more sensitive biomechanical tests (e.g. axial compressive tests) that may be needed for industrial applications, such as orthopaedic implant design.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Alexander Heidrich ◽  
Jana Schmidt ◽  
Johannes Zimmermann ◽  
Hans Peter Saluz

Background. Although chick embryogenesis has been studied extensively, there has been growing interest in the investigation of skeletogenesis. In addition to improved poultry health and minimized economic loss, a greater understanding of skeletal abnormalities can also have implications for human medicine. Truein vivostudies require noninvasive imaging techniques such as high-resolution microCT. However, the manual analysis of acquired images is both time consuming and subjective.Methods. We have developed a system for automated image segmentation that entails object-based image analysis followed by the classification of the extracted image objects. For image segmentation, a rule set was developed using Definiens image analysis software. The classification engine was implemented using the WEKA machine learning tool.Results. Our system reduces analysis time and observer bias while maintaining high accuracy. Applying the system to the quantification of long bone growth has allowed us to present the first truein ovodata for bone length growth recorded in the same chick embryos.Conclusions. The procedures developed represent an innovative approach for the automated segmentation, classification, quantification, and visualization of microCT images. MicroCT offers the possibility of performing longitudinal studies and thereby provides unique insights into the morpho- and embryogenesis of live chick embryos.


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