Effect of Biomechanical Environment on Degeneration of Meckel’s Cartilage

2020 ◽  
pp. 002203452096011
Author(s):  
M. Farahat ◽  
G.A.S. Kazi ◽  
E.S. Hara ◽  
T. Matsumoto
Keyword(s):  
Endochondral Ossification ◽  
Biomechanical Properties ◽  
Cartilage Degradation ◽  
Middle Region ◽  
Meckel's Cartilage ◽  
3 Dimensional ◽  
Meckel’S Cartilage ◽  
Surrounding Environment ◽  
Rigid Environment

During orofacial tissue development, the anterior and posterior regions of the Meckel’s cartilage undergo mineralization, while the middle region undergoes degeneration. Despite the interesting and particular phenomena, the mechanisms that regulate the different fates of Meckel’s cartilage, including the effects of biomechanical cues, are still unclear. Therefore, the purpose of this study was to systematically investigate the course of Meckel’s cartilage during embryonic development from a biomechanical perspective. Histomorphological and biomechanical (stiffness) changes in the Meckel’s cartilage were analyzed from embryonic day 12 to postnatal day 0. The results revealed remarkable changes in the morphology and size of chondrocytes, as well as the occurrence of chondrocyte burst in the vicinity of the mineralization site, an often-seen phenomenon preceding endochondral ossification. To understand the effect of biomechanical cues on Meckel’s cartilage fate, a mechanically tuned 3-dimensional hydrogel culture system was used. At the anterior region, a moderately soft environment (10-kPa hydrogel) promoted chondrocyte burst and ossification. On the contrary, at the middle region, a more rigid environment (40-kPa hydrogel) enhanced cartilage degradation by inducing a higher expression of MMP-1 and MMP-13. These results indicate that differences in the biomechanical properties of the surrounding environment are essential factors that distinctly guide the mineralization and degradation of Meckel’s cartilage and would be valuable tools for modulating in vitro cartilage and bone tissue engineering.

scholarly journals An in vitro investigation to understand the synergistic role of MMPs-1 and 9 on articular cartilage biomechanical properties

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Allison Mixon ◽  
Andrew Savage ◽  
Ahmed Suparno Bahar-Moni ◽  
Malek Adouni ◽  
Tanvir Faisal
Keyword(s):  
Peak Load ◽  
Biomechanical Properties ◽  
Cartilage Degradation ◽  
Enzyme Concentration ◽  
Cartilage Explants ◽  
Healthy State ◽  
In Vitro Investigation ◽  
Degradative Enzymes ◽  
The Impact

AbstractMatrix metalloproteinases (MMPs) play a crucial role in enzymatically digesting cartilage extracellular matrix (ECM) components, resulting in degraded cartilage with altered mechanical loading capacity. Overexpression of MMPs is often caused by trauma, physiologic conditions and by disease. To understand the synergistic impact MMPs have on cartilage biomechanical properties, MMPs from two subfamilies: collagenase (MMP-1) and gelatinase (MMP-9) were investigated in this study. Three different ratios of MMP-1 (c) and MMP-9 (g), c1:g1, c3:g1 and c1:g3 were considered to develop a degradation model. Thirty samples, harvested from bovine femoral condyles, were treated in groups of 10 with one concentration of enzyme mixture. Each sample was tested in a healthy state prior to introducing degradative enzymes to establish a baseline. Samples were subjected to indentation loading up to 20% bulk strain. Both control and treated samples were mechanically and histologically assessed to determine the impact of degradation. Young’s modulus and peak load of the tissue under indentation were compared between the control and degraded cartilage explants. Cartilage degraded with the c3:g1 enzyme concentration resulted in maximum 33% reduction in stiffness and peak load compared to the other two concentrations. The abundance of collagenase is more responsible for cartilage degradation and reduced mechanical integrity.

EGF abrogation-induced fusilli-form dysmorphogenesis of Meckel's cartilage during embryonic mouse mandibular morphogenesis in vitro

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 903-917 ◽  
Author(s):  
L. Shum ◽  
Y. Sakakura ◽  
P. Bringas ◽  
W. Luo ◽  
M.L. Snead ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Tooth Development ◽  
Branchial Arch ◽  
Abnormal Development ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Embryonic Mouse ◽  
Meckel's Cartilage ◽  
Meckel’S Cartilage

Mutations associated with genes of the EGF superfamily are implicated in facial malformations arising from abnormal development of the first branchial arch. EGF and EGF receptor (EGFr) transcripts are expressed in the mouse embryonic first branchial arch and derivatives from E9 through E15. EGF transcripts are localized to ectomesenchymal cells associated with precartilage, cartilage, bone and tooth-forming cells. EGF and EGFr proteins co-localize to the same cells suggesting an autocrine regulation. To test whether EGF effects the timing and positional information required for Meckel's cartilage (MC) and tooth development, we cultured E10 mandibular explants in serumless, chemically defined medium with either antisense or sense EGF oligodeoxynucleotides. Antisense inhibition of EGF expression produces bilaterally symmetrical Fusilli-form dysmorphogenesis of MC and decreases tooth bud size; these effects are reversed by the addition of exogenous EGF to the culture medium. Tyrphostin RG 50864, which inhibits EGF receptor kinase activity, inhibits EGF stimulation of tyrosine phosphorylation in a concentration-dependent manner and severely retards mandibular development yet increases tooth size. These findings support the hypothesis that endogenous EGF and EGF-like proteins provide signalling to regulate the size and shape both of cartilage and tooth formation during craniofacial morphogenesis.

Human 3-dimensional liver organoids: in vitro model systems to study liver diseases

2020 ◽  
Author(s):  
H Gaitantzi ◽  
C Cai ◽  
S Asawa ◽  
K Böttcher ◽  
M Ebert ◽  
...  
Keyword(s):  
Liver Diseases ◽  
In Vitro Model ◽  
Model Systems ◽  
3 Dimensional ◽  
Vitro Model ◽  
Liver Organoids

In vitro validation of a 3-dimensional transrectal ultrasound system for prostate biopsiess

2007 ◽  
Vol 30 (4) ◽  
pp. 77
Author(s):  
Derek Cool ◽  
Shi Sherebrin ◽  
Jonathan Izawa ◽  
Joseph Chin ◽  
Aaron Fenster
Keyword(s):  
Prostate Biopsy ◽  
3D Model ◽  
Transrectal Ultrasound ◽  
Surface Topology ◽  
Sufficient Information ◽  
Needle Guidance ◽  
3 Dimensional ◽  
High Incidence ◽  
3D Information

Introduction: Transrectal ultrasound (TRUS) prostate biopsy (Bx) is currently confined to 2D information to both target and record 3D Bx locations. Accurate placement of Bx needles cannot be verified without 3D information, and recording Bx sites in 2D does not provide sufficient information to accurately guide the high incidence of repeat Bx. We have designed a 3D TRUS prostate Bx system that augments the current 2D TRUS system and provides tools for biopsy-planning, needle guidance, and recording of the biopsy core locations entirely in 3D. Methods: Our Bx system displays a 3D model of the patient’s prostate, which is generated intra-procedure from a collection of 2D TRUS images, representative of the particular prostate shape. Bx targets are selected, needle guidance is facilitated, and 3D Bx sites are recorded within the 3D context of the prostate model. The complete 3D Bx system was validated, in vitro, by performing standard ten-core Bx on anatomical phantoms of two patient’s prostates. The accuracy of the needle-guidance, Bx location recording, and 3D model volume and surface topology were validated against a CT gold standard. Results: The Bx system successfully reconstructed the 3D patient prostate models with a mean volume error of 3.2 ± 7.6%. Using the 3D system, needles were accurately guided to the pre-determined targets with a mean error of 2.26 ± 1.03 mm and the 3D locations of the Bx cores were accurately recorded with a mean distance error of 1.47 ± 0.79 mm. Conclusion: We have successfully developed a 3D TRUS prostate biopsy system and validated the system in vitro. A pilot study has been initiated to apply the system clinically.

scholarly journals An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marisa Nacke ◽  
Emma Sandilands ◽  
Konstantina Nikolatou ◽  
Álvaro Román-Fernández ◽  
Susan Mason ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Cellular Responses ◽  
Signalling Pathways ◽  
External Signal ◽  
Phosphoinositide Metabolism ◽  
Invasion And Metastasis ◽  
3 Dimensional

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.

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