scholarly journals Axial mechanical loading to Ex Vivo mouse long bone regulates Endochondral ossification and Endosteal mineralization through activation of the BMP-Smad pathway during postnatal growth

Bone Reports ◽  
2021 ◽  
pp. 101088
Author(s):  
Satoshi Miyamoto ◽  
Hideki Yoshikawa ◽  
Ken Nakata
2017 ◽  
Vol 47 (8) ◽  
Author(s):  
Juliana Scarpa da Silveira Almeida ◽  
Débora de Oliveira Garcia ◽  
Renato Camargo Bortholin ◽  
Carlos Amaral Razzino ◽  
Cristiane dos Santos Honsho ◽  
...  

ABSTRACT: Long bone fractures are commonly in surgery routine and several bone imobilization techniques are currently available. Technological progress has enabled to use low cost materials in surgical procedures. Thus, the aim of this study was to evaluate the applicability of polyamide 12 rods, solid and hollow in swine femurs, comparing them through flexion strength. This study had as second aim to fix the locking errors, commom place in interlocking nails, once polyamide 12 allows perforation in any direction by orthopaedic screw. Six groups were used: G1 - eight whole swine femurs; G2 - eight whole swine femurs with drilled medullary canal; G3 - two solid polyamide 12 rods; G4 - two hollow polyamide 12 rods; G5 - eight osteotomized drilled swine femurs with a solid polyamide 12 rod implanted in the medullary canal and locked by four 316L stainless steel screws; and G6 - similar to G5 but using hollow rods instead of solid ones. No significant differences were observed for the modulus of rupture between solid and hollow rods, demonstrating that both rods had similar performances. These results led to the speculation that the addition of other polymers to the hollow rods could increase their strength and thus the bone-implant system. Furthermore, the comparison between G1, G5 and G6 could be analyzed using the finite element method in future. New polymeric materials may be developed based on the data from this study, strengthening the bone-implant system and making possible screws to be placed in any direction, nullifying the detrimental forces on the fracture site.


1999 ◽  
Vol 367 ◽  
pp. S356-S370 ◽  
Author(s):  
Albert J. Banes ◽  
Paul Weinhold ◽  
Xi Yang ◽  
Mari Tsuzaki ◽  
Donald Bynum ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ariane Zamarioli ◽  
Daniel A. Maranho ◽  
Mariana M. Butezloff ◽  
Patrícia A. Moura ◽  
José Batista Volpon ◽  
...  

To study the effects of mechanical loading on bones after SCI, we assessed macro- and microscopic anatomy in rats submitted to passive standing (PS) and electrical stimulation (ES). The study design was based on two main groups of juvenile male Wistar rats with SCI: one was followed for 33 days with therapies starting at day 3 and the other was followed for 63 days with therapies starting at day 33. Both groups were composed of four subgroups (n=10/group): (1) Sham, (2) SCI, (3) SCI + PS, and (4) SCI + ES. Rehabilitation protocol consisted of a 20-minute session, 3x/wk for 30 days. The animals were sequentially weighed and euthanized. The femur and tibia were assessed macroscopically and microscopically by scanning electronic microscopy (SEM). The SCI rats gained less weight than Sham-operated animals. Significant reduction of bone mass and periosteal radii was observed in the SCI rats, whereas PS and ES efficiently improved the macroscopic parameters. The SEM images showed less and thin trabecular bone in SCI rats. PS and ES efficiently ameliorated the bone microarchitecture deterioration by thickening and increasing the trabeculae. Based on the detrimental changes in bone tissue following SCI, the mechanical loading through weight bearing and muscle contraction may decrease the bone loss and restore the macro- and microanatomy.


2009 ◽  
Vol 463 (3) ◽  
pp. 254-257 ◽  
Author(s):  
Qiang Wu ◽  
Susannah J. Sample ◽  
Theresa A. Baker ◽  
Cathy F. Thomas ◽  
Mary Behan ◽  
...  

Author(s):  
Santiago Beltran Diaz ◽  
Chee Ho H’ng ◽  
Xinli Qu ◽  
Michael Doube ◽  
John Tan Nguyen ◽  
...  

The characterization of developmental phenotypes often relies on the accurate linear measurement of structures that are small and require laborious preparation. This is tedious and prone to errors, especially when repeated for the multiple replicates that are required for statistical analysis, or when multiple distinct structures have to be analyzed. To address this issue, we have developed a pipeline for characterization of long-bone length using X-ray microtomography (XMT) scans. The pipeline involves semi-automated algorithms for automatic thresholding and fast interactive isolation and 3D-model generation of the main limb bones, using either the open-source ImageJ plugin BoneJ or the commercial Mimics Innovation Suite package. The tests showed the appropriate combination of scanning conditions and analysis parameters yields fast and comparable length results, highly correlated with the measurements obtained via ex vivo skeletal preparations. Moreover, since XMT is not destructive, the samples can be used afterward for histology or other applications. Our new pipelines will help developmental biologists and evolutionary researchers to achieve fast, reproducible and non-destructive length measurement of bone samples from multiple animal species.


2019 ◽  
Author(s):  
S. Herberg ◽  
A. M. McDermott ◽  
P. N. Dang ◽  
D. S. Alt ◽  
R. Tang ◽  
...  

AbstractEndochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation and is directed by local morphogen signals and mechanical cues. Here, we aimed to mimic these developmental conditions for regeneration of large bone defects. We hypothesized that engineered human mesenchymal stem cell (hMSC) condensations with in situ presentation of transforming growth factor-β1 (TGF-β1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles would promote endochondral regeneration of critical-sized rat femoral bone defects in a manner dependent on the in vivo mechanical environment. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with dual BMP-2 + TGF-β1 fully restoring mechanical bone function by week 12. In vivo ambulatory mechanical loading, initiated at week 4 by delayed unlocking of compliant fixation plates, significantly enhanced the bone formation rate in the four weeks after load initiation in the dual morphogen group. In vitro, local presentation of either BMP-2 alone or BMP-2 + TGF-β1 initiated endochondral lineage commitment of mesenchymal condensations, inducing both chondrogenic and osteogenic gene expression through SMAD3 and SMAD5 signaling. In vivo, however, endochondral cartilage formation was evident only in the BMP-2 + TGF-β1 group and was enhanced by mechanical loading. The degree of bone formation was comparable to BMP-2 soaked on collagen but without the ectopic bone formation that limits the clinical efficacy of BMP-2/collagen. In contrast, mechanical loading had no effect on autograft-mediated repair. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.One Sentence SummaryMimicking aspects of the cellular, biochemical, and mechanical environment during early limb development, chondrogenically-primed human mesenchymal stem cell condensations promoted functional healing of critical-sized femoral defects via endochondral ossification, and healing rate and extent was a function of the in vivo mechanical environment.


2017 ◽  
Author(s):  
Brett S. Klosterhoff ◽  
Keat Ghee Ong ◽  
Laxminarayanan Krishnan ◽  
Kevin M. Hetzendorfer ◽  
Young-Hui Chang ◽  
...  

AbstractBone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure non-invasively. The objective of this work was to develop and characterize an implantable strain sensor for non-invasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, and in vivo demonstration of the device’s capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration. Ex vivo experimental characterization of the device showed that it exceeded the technical requirements for sensitivity, signal resolution, and electromechanical stability. The digital telemetry minimized power consumption, enabling long-term intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to non-invasively measure strain in real-time. Lastly, in vivo strain measurements were utilized in a finite element model to estimate the strain distribution within the defect region. Together, these data indicate the sensor is a promising technology to quantify local tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic skeletal healing and remodeling.


2021 ◽  
Author(s):  
Susan M. Motch Perrine ◽  
M Kathleen Pitirri ◽  
Emily L Durham ◽  
Mizuho Kawasaki ◽  
Hao Zheng ◽  
...  

The cranial endo- and dermal skeletons, which comprise the vertebrate skull, evolved independently and form separately during embryogenesis. In mammals, the mostly cartilaginous cranial endoskeleton forms prior to the bony dermatocranium. Many features of the chondrocranium are transient, undergoing endochondral ossification or disappearing, so its role in skull morphogenesis is not understood The fibroblast growth factor (FGF) and receptor (FGFR) signaling pathway contributes significantly to the regulation of osteochondroprogenitor cell function. Mutations in FGFR genes are associated with diseases that impact the skull including dwarfing chondrodyplasia and craniosynostosis syndromes. We investigate the developing chondrocranium and dermatocranium using a mouse model for craniosynostosis carrying a gain of function mutation in Fgfr2 to assess development of these cranial skeleton systems. Dermatocrania and chondrocrania of Fgfr2cC342Y/+ mice and their Fgfr2c+/+ littermates were quantified in 3D from microcomputed tomography images of mouse embryos. Chondrocrania of embryonic mice carrying the Fgfr2 mutation are larger than their Fgfr2c+/+ littermates and include novel extensions of cartilage over the lateral and dorsal aspect of the brain. Like the forming chondrocranium, the embryonic dermatocranium is larger in Fgfr2cC342Y/+ mice throughout embryogenesis but after disappearance of much of the chondrocranium, the dermatocranium becomes progressively smaller relative to Fgfr2c+/+ littermates during postnatal growth. Results reveal the direct effects of this Fgfr2c mutation on embryonic cranial cartilage, the impact of chondrocranial structure on developing dermatocranial elements, the importance of the chondrocranium in decoding the impact of specific genetic variants on head morphogenesis, and the potential for harnessing these effects as therapeutic targets.


2017 ◽  
Author(s):  
Albert Kwok ◽  
Ilona Zvetkova ◽  
Sam Virtue ◽  
Isabel Huang-Doran ◽  
Patsy Tomlinson ◽  
...  

SummaryHeterodimeric class IA phosphatidylinositol-3-kinases (PI3K) transduce signals from many receptor tyrosine kinases including the insulin receptor. PI3K recruitment to phosphotyrosines is mediated by Pik3r1 gene products including the most intensely studied PI3K regulatory subunit, p85α, which also binds and regulates the PIP3 phosphatase Pten, and the lipogenic transcription factor Xbp1. Mutations in human PIK3R1 cause SHORT syndrome, featuring lipodystrophy and severe insulin resistance which, uniquely, are uncoupled from fatty liver and dyslipidemia. We describe a novel mouse model of SHORT syndrome made by knock in of the Pik3r1 Y657X mutation. Homozygous embryos die at E11.5, while heterozygous mice exhibit pre-and postnatal growth impairment with diminished placental vascularity. Adipose tissue accretion on high fat feeding was reduced, however adipocyte size was unchanged and preadipocyte differentiation ex vivo unimpaired. Despite severe insulin resistance, heterozygous mice were hypolipidemic, and plasma adiponectin, liver weight, cholesterol, glycogen and triglyceride content were unchanged. Mild downregulation of lipogenic Srebp1, Srebp2 and Chrebp transcriptional activity but no suppression of Xbp1 target genes was seen after fasting. These findings give new insights into the developmental role of Pik3r1, and establish a model of lipodystrophic insulin resistance dissociated from dyslipidemia as seen in SHORT syndrome.


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