scholarly journals Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation

2019 ◽  
Vol 20 (13) ◽  
pp. 3147 ◽  
Author(s):  
Sun-Ju Yi ◽  
Hyerim Lee ◽  
Jisu Lee ◽  
Kyubin Lee ◽  
Junil Kim ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Bone Cells ◽  
Bone Development ◽  
Bone Cell ◽  
Gene Expressions ◽  
Chromatin Dynamics ◽  
Multinucleated Cells ◽  
Bone Cell Differentiation ◽  
Fate Determinants ◽  
The Impact

The bone tissue is a dynamic complex that constitutes of several interdependent systems and is continuously remodeled through the concerted actions of bone cells. Osteoblasts are mononucleated cells, derived from mesenchymal stem cells, responsible for bone formation. Osteoclasts are large multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage and are responsible for bone resorption. The lineage-specific differentiation of bone cells requires an epigenetic regulation of gene expressions involving chromatin dynamics. The key step for understanding gene regulatory networks during bone cell development lies in characterizing the chromatin modifying enzymes responsible for reorganizing and potentiating particular chromatin structure. This review covers the histone-modifying enzymes involved in bone development, discusses the impact of enzymes on gene expression, and provides future directions and clinical significance in this area.

scholarly journals Minireview: Transcriptional Regulation in Development of Bone

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1012-1017 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Henry Kronenberg
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Bone Cells ◽  
Genetic Manipulation ◽  
Bone Development ◽  
Regulation Of Gene Expression ◽  
Bone Cell ◽  
Cellular Functions ◽  
Multiple Differentiation

Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone.

scholarly journals Origins of Alterations to Rankl Null Mutant Mouse Dental Root Development

2020 ◽  
Vol 21 (6) ◽  
pp. 2201
Author(s):  
Andrea Gama ◽  
Jorge William Vargas-Franco ◽  
Diana Carolina Sánchez Mesa ◽  
Elizabeth Restrepo Bedoya ◽  
Jérome Amiaud ◽  
...  
Keyword(s):  
Root Development ◽  
Alveolar Bone ◽  
Bone Cells ◽  
Cell Communication ◽  
Neutralizing Antibody ◽  
Bone Cell ◽  
Experimental Models ◽  
Nuclear Antigen ◽  
Bone Cell Differentiation ◽  
Proliferating Cell

The purpose of the present study was to assess the early stages of development of mouse first molar roots in the osteopetrotic context of RANKL invalidation in order to demonstrate that the radicular phenotype observed resulted not only from defective osteoclasts, but also from loss of cell-to-cell communication among dental, periodontium and alveolar bone cells involving RANKL signaling. Two experimental models were used in this study: Rankl mutants with permanent RANKL invalidation, and C57BL/6J mice injected during the first postnatal week with a RANKL neutralizing antibody corresponding to a transient RANKL invalidation. The dento-alveolar complex was systematically analyzed using micro-CT, and histological and immunohistochemical approaches. These experiments showed that the root elongation alterations observed in the Rankl-/- mice were associated with reduced proliferation of the RANK-expressing HERS cells with a significant decrease in proliferating cell nuclear antigen (PCNA) expression and a significant increase in P21 expression. The phenotypic comparison of the adult first molar root at 35 days between permanent and transitory invalidations of RANKL made it possible to demonstrate that alterations in dental root development have at least two origins, one intrinsic and linked to proliferation/differentiation perturbations in dental-root-forming cells, the other extrinsic and corresponding to disturbances of bone cell differentiation/function.

scholarly journals Gene network simulations provide testable predictions for the molecular domestication syndrome

2021 ◽  
Author(s):  
Ewen Burban ◽  
Maud Irene Tenaillon ◽  
Arnaud Le Rouzic
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Environmental Stability ◽  
Interaction Matrix ◽  
Gene Expressions ◽  
Domestication Syndrome ◽  
Molecular Domestication ◽  
Gene Regulatory ◽  
The Impact

The domestication of plant and animal species lead to repeatable morphological evolution, often referred to as the phenotypic domestication syndrome. Domestication is also associated with important genomic changes, such as the loss of genetic diversity and modifications of gene expression patterns. Here, we explored theoretically the effect of domestication at the genomic level by characterizing the impact of a domestication-like scenario on gene regulatory networks. We ran population genetics simulations in which individuals were featured by their genotype (an interaction matrix encoding a gene regulatory network) and their gene expressions, representing the phenotypic level. Our domestication scenario included a population bottleneck and a selection switch (change in the optimal gene expression level) mimicking canalizing selection, i.e. evolution towards more stable expression to parallel enhanced environmental stability in man-made habitat. We showed that domestication profoundly alters genetic architectures. Based on the well-documented example of the maize (Zea mays ssp. mays) domestication, our simulations predicted (i) a drop in neutral allelic diversity, (ii) a change in gene expression variance that depended upon the domestication scenario, (iii) transient maladaptive plasticity, (iv) a deep rewiring of the gene regulatory networks, with a trend towards gain of regulatory interactions between genes, and (v) a global increase in the genetic correlations among gene expressions, with a loss of modularity in the resulting coexpression patterns and in the underlying networks. Extending the range of parameters, we provide empirically testable predictions on the differences of genetic architectures between wild and domesticated and forms. The characterization of such systematic evolutionary changes in the genetic architecture of traits contributes to define a molecular domestication syndrome.

Raman Spectroscopy: Potential Tool for In-Situ Characterization of Bone Cell Differentiation

2005 ◽  
Vol 284-286 ◽  
pp. 545-548 ◽  
Author(s):  
Ioan Notingher ◽  
G. Jell ◽  
P.L. Notingher ◽  
I. Bisson ◽  
Julia M. Polak ◽  
...  
Keyword(s):  
Raman Spectra ◽  
Bone Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Bone Cell ◽  
Least Square ◽  
Fitting Method ◽  
Bone Cell Differentiation

The Classical Least Square (CLS) fitting method was used to analyze the Raman spectra of living cells with the aim of identification of new phenotype-specific spectral markers for osteoblasts. The following chemicals were used for the CLS model: DNA, RNA, serum albumin, chymotrypsin and phosphatidyl choline. In this study we analyzed primary mature osteoblasts as well as two other cell types used as potential sources of osteoblasts: embryonic stem cells and fetal bone cells. The results obtained suggest that the Raman spectra of the cell types can be well approximated with a linear combination of the Raman spectra of the biopolymers used in the CLS model. The relative concentrations of the CLS components varied significantly between cell types, indicating that this analytical method could be used for phenotypic identification of osteoblasts.

scholarly journals Molecular Basis of Bone Aging

2020 ◽  
Vol 21 (10) ◽  
pp. 3679 ◽  
Author(s):  
Addolorata Corrado ◽  
Daniela Cici ◽  
Cinzia Rotondo ◽  
Nicola Maruotti ◽  
Francesco Paolo Cantatore
Keyword(s):  
Animal Studies ◽  
Molecular Mechanisms ◽  
Bone Cells ◽  
Current Knowledge ◽  
Cellular Tissue ◽  
Bone Cell ◽  
Age Related ◽  
Bone Cell Differentiation ◽  
Bone Changes

A decline in bone mass leading to an increased fracture risk is a common feature of age-related bone changes. The mechanisms underlying bone senescence are very complex and implicate systemic and local factors and are the result of the combination of several changes occurring at the cellular, tissue and structural levels; they include alterations of bone cell differentiation and activity, oxidative stress, genetic damage and the altered responses of bone cells to various biological signals and to mechanical loading. The molecular mechanisms responsible for these changes remain greatly unclear and many data derived from in vitro or animal studies appear to be conflicting and heterogeneous, probably due to the different experimental approaches; nevertheless, understanding the main physio-pathological processes that cause bone senescence is essential for the development of new potential therapeutic options for treating age-related bone loss. This article reviews the current knowledge concerning the molecular mechanisms underlying the pathogenesis of age-related bone changes.

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

scholarly journals Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neel Patel ◽  
William S. Bush
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Prediction Models ◽  
Long Distance ◽  
Chromatin Looping ◽  
Gene Regulatory ◽  
The Impact

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

Heat Generation in Bone Cutting-Implications for Thermal Necrosis

2001 ◽  
Author(s):  
Debra Chenet Millon ◽  
Darren L. Hitt ◽  
Stephan J. LaPointe
Keyword(s):  
Bone Cells ◽  
Heat Exposure ◽  
Fibrous Tissue ◽  
Metatarsal Head ◽  
Bone Cell ◽  
Frictional Heat ◽  
Fat Cell ◽  
Critical Temperatures ◽  
Cell Degeneration ◽  
Prolonged Heat

Abstract A bunion is a common foot disorder caused by an abnormal outward projection of the joint and inward turning of the toe. Surgery to correct the malformation involves cutting the first metatarsal head, repositioning and setting it; the bone is then left to heal itself over time. A potentially serious by-product of the bone cutting is the frictional heat generated. While the heat susceptibility of individual bone cells varies throughout bone and is difficult to quantify, studies have shown that when injured, bone may not always heal as bone but rather as a fibrous tissue of varying degrees of differentiation. Prolonged heat exposure at or above critical temperatures may also lead to fat and bone cell resorption, a subsequent fat cell degeneration of the tissue, local swelling of cells as well as denaturation of the enzymatic and membrane proteins (Eriksson & Albrektsson, 1983, Li et al, 1999).

Morphological studies of bone and tendon

1992 ◽  
Vol 73 (2) ◽  
pp. S10-S13 ◽  
Author(s):  
S. B. Doty ◽  
E. R. Morey-Holton ◽  
G. N. Durnova ◽  
A. S. Kaplansky
Keyword(s):  
Electron Microscopy ◽  
Bone Cells ◽  
Weight Bearing ◽  
Light And Electron Microscopy ◽  
Cell Activity ◽  
Bone Cell ◽  
Electron Microscopic ◽  
Adult Rats ◽  
Morphological Studies ◽  
Metatarsal Bones

The Soviet biosatellite COSMOS 2044 carried adult rats on a spaceflight that lasted 13.8 days and was intended to repeat animal studies carried out on COSMOS 1887. Skeletal tissue and tendon from animals flown on COSMOS 2044 were studied by light and electron microscopy, histochemistry, and morphometric techniques. Studies were confined to the bone cells and vasculature from the weight-bearing tibias. Results indicated that vascular changes at the periosteal and subperiosteal region of the tibia were not apparent by light microscopy or histochemistry. However, electron microscopy indicated that vascular inclusions were present in bone samples from the flight animals. A unique combination of microscopy and histochemical techniques indicated that the endosteal osteoblasts from this same mid-diaphyseal region demonstrated a slight (but not statistically significant) reduction in bone cell activity. Electron-microscopic studies of the tendons from metatarsal bones showed a collagen fibril disorganization as a result of spaceflight. Thus changes described for COSMOS 1887 were present in COSMOS 2044, but the changes ascribed to spaceflight were not as evident.

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