Effect of Mechanical Loading On Periodontal Cells

2001 ◽  
Vol 12 (5) ◽  
pp. 414-424 ◽  
Author(s):  
Dubravko Pavlin ◽  
Jelica Gluhak-Heinrich
Keyword(s):  
Cell Culture ◽  
Animal Models ◽  
Mechanical Loading ◽  
Alveolar Bone ◽  
Bone Sialoprotein ◽  
Collagen I ◽  
Bone Homeostasis ◽  
In Vivo Models ◽  
Stimulation Of

Mechanical loading is an important regulatory factor in alveolar bone homeostasis, and plays an essential role in maintaining the structure and mass of the alveolar processes throughout lifetime. A better understanding of the cellular and molecular responses of periodontal cells is a prerequisite for further improvements of therapeutic approaches in orthodontics, periodontal and alveolar bone repair and regeneration, implantology, and post-surgical wound healing. The purpose of this review is to provide an insight into some cell culture and animal models used for studying the effects of mechanical loading on periodontal cells, and into the recent developments and utilization of new in vivo animal models. There has been an increased awareness about the need for improvement and development of in vivo models to supplement the widely used cell culture models, and for biological validation of in vitro results, especially in the light of evidence that developmental models may not always reflect bone homeostasis in an adult organism. Due to the limitations of in vivo models, previous studies on mechanical regulation of alveolar bone osteoblasts and cementoblasts mostly focused on proliferative responses, rather than on the stimulation of cell differentiation. To address this problem, we have recently characterized and implemented a mouse osteoinductive tooth movement model for studying mechanically induced regulation of osteoblast- and cementoblast-associated genes. In this model, a defined and reproducible mechanical osteogenic loading is applied during a time course of up to two weeks. Regulation of gene expression in either wild-type or transgenic animals is assessed by a relative quantitative measurement of the level of target mRNAs directly within the subpopulations of periodontal cells. To date, results demonstrate a defined temporal pattern of cell-specific gene regulation in periodontal osteoblasts mechanically stimulated to differentiate and deposit bone matrix. The responses of osteoblast-associated genes to mechanical loading were 10- to 20-fold greater than the increase in the numbers of these cells, indicating that the induction of differentiation and an increase of cell function are the primary responses to osteogenic loading. The progression of the osteoblast phenotype in the intact mouse periodontium was several-fold faster compared with that in cultured cells, suggesting that the mechanical signal may be targeting osteoblast precursors in the state of readiness to respond to an environmental challenge, without the initial proliferative response. An early response of alkaline phosphatase and bone sialoprotein genes was detected after 24 hrs of treatment, followed by a concomitant stimulation of osteocalcin and collagen I between 24 and 48 hrs, and deposition of osteoid after 72 hrs. Although cementoblasts constitutively express biochemical markers similar to those of osteoblasts, distinct responses of osteocalcin, collagen I, and bone sialoprotein genes to mechanical loading were observed in the two cell phenotypes. This finding indicates that differential genetic responses to mechanical loading provide functional markers for distinction of the cementoblast and osteoblast phenotypes.

scholarly journals Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Zachary Fralish ◽  
Ethan M. Lotz ◽  
Taylor Chavez ◽  
Alastair Khodabukus ◽  
Nenad Bursac
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Animal Models ◽  
Schwann Cells ◽  
Motor Neurons ◽  
Small Animal ◽  
In Vivo Models ◽  
Small Animal Models

The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.

scholarly journals The transcriptional landscape of a hepatoma cell line grown on scaffolds of extracellular matrix proteins

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Souvik Ghosh ◽  
Anastasiya Börsch ◽  
Shreemoyee Ghosh ◽  
Mihaela Zavolan
Keyword(s):  
Cell Culture ◽  
Extracellular Matrix ◽  
Drug Targets ◽  
Hepatoma Cell ◽  
Growth Potential ◽  
Collagen I ◽  
Matrix Proteins ◽  
Hepatoma Cell Line ◽  
Primary Hepatocytes

Abstract Background The behavior of cells in vivo is complex and highly dynamic, as it results from an interplay between intercellular matrix proteins with surface receptors and other microenvironmental cues. Although the effects of the cellular niche have been investigated for a number of cell types using different molecular approaches, comprehensive assessments of how the global transcriptome responds to 3D scaffolds composed of various extracellular matrix (ECM) constituents at different concentrations are still lacking. Results In this study, we explored the effects of two diverse extracellular matrix (ECM) components, Collagen I and Matrigel, on the transcriptional profile of cells in a cell culture system. Culturing Huh-7 cells on traditional cell culture plates (Control) or on the ECM components at different concentrations to modulate microenvironment properties, we have generated transcriptomics data that may be further explored to understand the differentiation and growth potential of this cell type for the development of 3D cultures. Our analysis infers transcription factors that are most responsible for the transcriptome response to the extracellular cues. Conclusion Our data indicates that the Collagen I substrate induces a robust transcriptional response in the Huh-7 cells, distinct from that induced by Matrigel. Enhanced hepatocyte markers (ALB and miR-122) reveal a potentially robust remodelling towards primary hepatocytes. Our results aid in defining the appropriate culture and transcription pathways while using hepatoma cell lines. As systems mimicking the in vivo structure and function of liver cells are still being developed, our study could potentially circumvent bottlenecks of limited availability of primary hepatocytes for preclinical studies of drug targets.

A Novel Peptide Aldehyde with Activity against Human Cytomegalovirus in Two Different in Vivo Models

2000 ◽  
Vol 11 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Olaf Weber ◽  
Jürgen Reefschläger ◽  
Helga Rübsamen-Waigmann ◽  
Siegfried Raddatz ◽  
Matthias Hesseling ◽  
...  
Keyword(s):  
Animal Models ◽  
Antiviral Activity ◽  
Clinical Isolate ◽  
Human Cytomegalovirus ◽  
Murine Cytomegalovirus ◽  
Human Tissues ◽  
In Vivo Models ◽  
Peptide Aldehydes

Novel peptide aldehydes (PAs) were identified as potent inhibitors of human cytomegalovirus (HCMV) in vitro. Although these compounds were highly effective against HCMV, they did not exhibit any activity against murine cytomegalovirus (MCMV). The purpose of this study was to test the antiviral activity of PA 8 as a representative of this novel class of inhibitors against HCMV in vivo. Because of the strict species specificity of HCMV we had to use two artificial animal models. In the first model, HCMV-infected human cells were entrapped into agarose plugs and transplanted into mice. In the second model, SCID mice were transplanted with human tissues that were subsequently infected with a clinical isolate of HCMV. In these two models the antiviral activity of PA 8 was clearly demonstrated, ganciclovir only being slightly superior in its in vivo antiviral activity.

In Vivo Models of Mechanical Loading

2019 ◽  
pp. 369-390 ◽  
Author(s):  
Behzad Javaheri ◽  
Nathalie Bravenboer ◽  
Astrid D. Bakker ◽  
Albert van der Veen ◽  
Roberto Lopes de Souza ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
In Vivo Models

scholarly journals In Vivo Models for Cholangiocarcinoma—What Can We Learn for Human Disease?

2020 ◽  
Vol 21 (14) ◽  
pp. 4993 ◽  
Author(s):  
Raphael Mohr ◽  
Burcin Özdirik ◽  
Jana Knorr ◽  
Alexander Wree ◽  
Münevver Demir ◽  
...  
Keyword(s):  
Animal Models ◽  
Human Disease ◽  
Liver Tumors ◽  
Tumor Biology ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Primary Liver Tumors ◽  
Stromal Microenvironment

Cholangiocarcinoma (CCA) comprises a heterogeneous group of primary liver tumors. They emerge from different hepatic (progenitor) cell populations, typically via sporadic mutations. Chronic biliary inflammation, as seen in primary sclerosing cholangitis (PSC), may trigger CCA development. Although several efforts were made in the last decade to better understand the complex processes of biliary carcinogenesis, it was only recently that new therapeutic advances have been achieved. Animal models are a crucial bridge between in vitro findings on molecular or genetic alterations, pathophysiological understanding, and new therapeutic strategies for the clinic. Nevertheless, it is inherently difficult to recapitulate simultaneously the stromal microenvironment (e.g., immune-competent cells, cholestasis, inflammation, PSC-like changes, fibrosis) and the tumor biology (e.g., mutational burden, local growth, and metastatic spread) in an animal model, so that it would reflect the full clinical reality of CCA. In this review, we highlight available data on animal models for CCA. We discuss if and how these models reflect human disease and whether they can serve as a tool for understanding the pathogenesis, or for predicting a treatment response in patients. In addition, open issues for future developments will be discussed.

scholarly journals Mechanical loading regulates expression of talin and its mRNA, which are concentrated at myotendinous junctions

1998 ◽  
Vol 275 (3) ◽  
pp. C818-C825 ◽  
Author(s):  
Jérôme Frenette ◽  
James G. Tidball
Keyword(s):  
Mechanical Loading ◽  
In Vivo Model ◽  
Proteolytic Fragment ◽  
In Vivo Models ◽  
Hindlimb Muscles ◽  
Vitro Model ◽  
Model C ◽  
Myotendinous Junctions

The hypothesis that mechanical loading regulates talin expression in developing and adult muscle was tested using in vitro and in vivo models. Talin was selected for study because it is a key structural link between the cytoskeleton and cell membrane. In the in vitro model, C2C12myotubes were subjected to cyclic strains for 48 h. In the in vivo model, rat hindlimb muscles were unloaded for 10 days, then reloaded for 2 days. Cyclic loading of myotubes resulted in significant increases in the quantity of talin (68%) and its 190-kDa proteolytic fragment (70%), as well as talin mRNA (180%), relative to unloaded myotube cultures. Similarly, talin concentration and its mRNA increased by 68 and 136%, respectively, in soleus muscles reloaded for 2 days relative to ambulatory controls. Immunohistochemistry and in situ RT-PCR showed that talin and its mRNA are concentrated and colocalized at myotendinous junctions. Thus these findings indicate that increased mechanical loading promotes talin synthesis, which occurs principally at myotendinous junctions, according to talin mRNA distribution.

scholarly journals Animal Models of Zika Virus Infection during Pregnancy

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 598 ◽  
Author(s):  
Elizabeth Caine ◽  
Brett Jagger ◽  
Michael Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Congenital Abnormalities ◽  
Tissue Tropism ◽  
Zikv Infection ◽  
In Vivo Models ◽  
Sexually Transmitted

Zika virus (ZIKV) emerged suddenly in the Americas in 2015 and was associated with a widespread outbreak of microcephaly and other severe congenital abnormalities in infants born to mothers infected during pregnancy. Vertical transmission of ZIKV in humans was confirmed when viral RNA was detected in fetal and placental tissues, and this outcome has been recapitulated experimentally in animals. Unlike other flaviviruses, ZIKV is both arthropod- and sexually-transmitted, and has a broad tissue tropism in humans, including multiple tissues of the reproductive tract. The threats posed by ZIKV have prompted the development of multiple in vivo models to better understand the pathogenesis of ZIKV, particularly during pregnancy. Here, we review the progress on animal models of ZIKV infection during pregnancy. These studies have generated a foundation of insights into the biology of ZIKV, and provide a means for evaluating vaccines and therapeutics.

scholarly journals In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents

Ulcers ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Michael Buenor Adinortey ◽  
Charles Ansah ◽  
Isaac Galyuon ◽  
Alexander Nyarko
Keyword(s):  
Peptic Ulcer ◽  
Animal Models ◽  
Gastrointestinal Diseases ◽  
Experimental Models ◽  
Lower Side ◽  
In Vivo Models ◽  
Biochemical Basis ◽  
Lead Compounds ◽  
Antiulcer Drugs

Peptic ulcer is among the most serious gastrointestinal diseases in the world. Several orthodox drugs are employed for the treatment of the disease. Although these drugs are effective, they produce many adverse effects thus limiting their use. In recent years, there has been a growing interest in alternative therapies, especially those from plants due to their perceived relative lower side effects, ease of accessibility, and affordability. Plant medicines with ethnomedicinal use in peptic ulcer management need to be screened for their effectiveness and possible isolation of lead compounds. This requires use of appropriate animal models of various ulcers. The limited number of antiulcer models for drug development against gastric and duodenal ulcer studies has hindered the progress of targeted therapy in this field. It is, therefore, necessary to review the literature on experimental models used to screen agents with potential antigastroduodenal ulcer activity and explain their biochemical basis in order to facilitate their use in the development of new preventive and curative antiulcer drugs. Clinical trials can then be carried out on agents/drugs that show promise. In this paper, current in vivo animal models of ulcers and the pathophysiological mechanisms underlying their induction, their limitations, as well as the challenges associated with their use have been discussed.

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