39 research outputs found
Dentofacial Changes in Patients with Class III Malocclusions Treated By a Combination of Activator and Chin-Cup Appliances
The purpose of this study was to examine, on pre-treatment and post-treatment lateral cephalograms, the effects of combined activator/chincup therapy on Class III patients, and to compare mean cephalometric diferences noted during treatment with untreated Class I suhjects. Fourteen females and fifteen males who exhibited a Class III malocclusion were the subjects of the study. Direct comparison of the mean value changes of the cephalometric variables during treatment of Class III patients with untreated Class I subjects revealed that SNA increased more and SNB increased less in the Class III patients than in the control group, thus improving the ANB angle. At the end of treatment, all patients had a positive overjet but a more concave profile. In this study, combined activator/chin-cup therapy seemed to induce improvement in those Class III patients selected for their moderate condition and treated over a five-year period. The changes seemed to indicate growth patterns which imitate those of the untreated Class I subjects. Moreover, dentoalveolar compensations helped to improve the overjet and conceal skeletal deviations
Mechanotransduction pathways in bone pathobiology
The skeleton is subject to dynamic changes throughout life and bone
remodeling is essential for maintenance of bone functionality. The cell
populations which predominantly participate in bone and cartilage
remodeling, namely osteocytes, osteoblasts, osteodasts and chondrocytes
sense and respond to external mechanical signals and via a series of
molecular cascades control bone metabolism and turnover rate. The
aforementioned process, known as mechanotransduction, is the underlying
mechanism that controls bone homeostasis and function. A wide array of
cross-talking signaling pathways has been found to play an important
role in the preservation of bone and cartilage tissue health. Moreover,
alterations in bone mechanotransduction pathways, due to genetic,
hormonal and biomechanical factors, are considered responsible for the
pathogenesis of bone and cartilage diseases. Extensive research has been
conducted and demonstrated that aberrations in mechanotransduction
pathways result in disease-like effects, however only few signaling
pathways have actually been engaged in the development of bone disease.
The aim of the present review is to present these signaling molecules
and cascades that have been found to be mechano-responsive and
implicated in bone disease development, as revealed by research in the
last five years. In addition, the role of these molecules as prognostic
or diagnostic disease markers and their potential as therapeutic targets
are also discussed. (C) 2015 Elsevier B.V. All rights reserved
Mechanotransduction pathways in bone pathobiology
AbstractThe skeleton is subject to dynamic changes throughout life and bone remodeling is essential for maintenance of bone functionality. The cell populations which predominantly participate in bone and cartilage remodeling, namely osteocytes, osteoblasts, osteoclasts and chondrocytes sense and respond to external mechanical signals and via a series of molecular cascades control bone metabolism and turnover rate. The aforementioned process, known as mechanotransduction, is the underlying mechanism that controls bone homeostasis and function. A wide array of cross-talking signaling pathways has been found to play an important role in the preservation of bone and cartilage tissue health. Moreover, alterations in bone mechanotransduction pathways, due to genetic, hormonal and biomechanical factors, are considered responsible for the pathogenesis of bone and cartilage diseases. Extensive research has been conducted and demonstrated that aberrations in mechanotransduction pathways result in disease-like effects, however only few signaling pathways have actually been engaged in the development of bone disease. The aim of the present review is to present these signaling molecules and cascades that have been found to be mechano-responsive and implicated in bone disease development, as revealed by research in the last five years. In addition, the role of these molecules as prognostic or diagnostic disease markers and their potential as therapeutic targets are also discussed
Polycystin-1: Function as a mechanosensor
Polycystin-1 (PC1), encoded by the Pkd1 gene, is a large transmembrane
protein whose mutation is involved in autosomal dominant polycystic
kidney disease. When expressed, PC1 activates a G-protein signaling
pathway that subsequently modulates Ca2+. channels. PC1 is highly
expressed in developing tissue and via its C-terminus tail forms a
complex with polycystin-2; this complex, found to be located at the
primary cilia, seems to act as a mechanosensor that could affect
proliferation, differentiation and apoptosis of cells. Also, loss of
polycystins correlates with disruption of flow-dependent and
steady-state intracellular Ca2+. signaling. Despite the lack of clarity
on the role of the polycystins as mechanosensor molecules, a new
interest in this PCs/primary cilium complex is providing continuously
new insights. In this review, some of the known features of PC1 such as
structure, function, signaling pathways involved and its role as a
possible therapeutic target are being discussed. (c) 2010 Elsevier Ltd.
All rights reserved
Polycystins in Colorectal Cancer
Cell and extracellular matrix (ECM) biomechanics emerge as a distinct
feature during the development and progression of colorectal cancer
(CRC). Polycystins are core mechanosensitive protein molecules that
mediate mechanotransduction in a variety of epithelial cells.
Polycystin-1 (PC1) and polycystin-2 (PC2) are engaged in signal
transduction mechanisms and during alterations in calcium influx, which
regulate cellular functions such as proliferation, differentiation,
orientation, and migration in cancer cells. Recent findings implicate
polycystins in the deregulation of such functions and the formation of
CRC invasive phenotypes. Polycystins participate in all aspects of the
cell's biomechanical network, from the perception of extracellular
mechanical cues to focal adhesion protein and nuclear transcriptional
complexes. Therefore, polycystins could be employed as novel biomarkers
and putative targets of selective treatment in CRC
MicroRNAs in Colorectal Neoplasia: From Pathobiology to Clinical Applications
MicroRNAs (miRNAs) are small, non-coding RNAs that can
post-transcriptionally regulate gene expression via messenger RNA (mRNA)
targeting. During the past few years several miRNA groups emerged as
critical components of developmental and pathological processes, among
them being cancer. In colorectal cancer (CRC) specifically, numerous
miRNA molecules have been identified up-or downregulated functioning as
tumor-specific markers with oncogenic and tumor-suppressive properties.
Their dysregulation impacts impaired cellular processes such as cell
proliferation, apoptosis, angiogenesis, invasion and metastasis. The
detection of extracellular miRNAs in plasma and fecal samples of CRC
patients tends to provide novel, non-invasive biomarkers in favor of CRC
diagnosis and, at the same time, data from in vivo and in vitro CRC
models reveal promising therapeutic applications through miRNA
inhibition and miRNA delivery
Polycystins in Colorectal Cancer
Cell and extracellular matrix (ECM) biomechanics emerge as a distinct feature during the development and progression of colorectal cancer (CRC). Polycystins are core mechanosensitive protein molecules that mediate mechanotransduction in a variety of epithelial cells. Polycystin-1 (PC1) and polycystin-2 (PC2) are engaged in signal transduction mechanisms and during alterations in calcium influx, which regulate cellular functions such as proliferation, differentiation, orientation, and migration in cancer cells. Recent findings implicate polycystins in the deregulation of such functions and the formation of CRC invasive phenotypes. Polycystins participate in all aspects of the cell’s biomechanical network, from the perception of extracellular mechanical cues to focal adhesion protein and nuclear transcriptional complexes. Therefore, polycystins could be employed as novel biomarkers and putative targets of selective treatment in CRC
Solid Cancers and Rheumatoid Arthritis
Since the initial observation that patients with rheumatoid arthritis (RA) have an excess risk of developing hematologic malignancies [...
DNA methylation biomarkers as diagnostic and prognostic tools in colorectal cancer
Colorectal cancer (CRC) is the third most common type of cancer and is
responsible for 9 % of cancer deaths in both men and women in the USA
for 2013. It is a heterogenous disease, and its three classification
types are microsatellite instability, chromosomal instability, and CpG
island methylator phenotype. Biomarkers are molecules, which can be used
as indicators of cancer. They have the potential to achieve great
sensitivities and specificities in diagnosis and prognosis of CRC. DNA
methylation biomarkers are epigenetic markers, more specifically genes
that become silenced after aberrant methylation of their promoter in
CRC. Some methylation biomarkers like SEPT9 (ColoVantageA (R)) and
vimentin (ColoSure(TM)) are already commercially available. Other blood
and fecal-based biomarkers are currently under investigation and
clinical studies so that they can be used in the near future. Biomarker
panels are also currently being studied since they show great potential
in diagnosis as they can combine robust biomarkers to achieve even
greater sensitivities than single markers. Finally,
methylation-sensitive microRNAs (miRNAs) are very promising markers, and
their investigation as biomarkers, is only at primitive stage
Signaling mechanisms implicated in cranial sutures pathophysiology: Craniosynostosis
Normal extension and skull expansion is a synchronized process that prevails along the osteogenic intersections of the cranial sutures. Cranial sutures operate as bone growth sites allowing swift bone generation at the edges of the bone fronts while they remain patent. Premature fusion of one or more cranial sutures can trigger craniosynostosis, a birth defect characterized by dramatic manifestations in appearance and functional impairment. Up until today, surgical correction is the only restorative measure for craniosynostosis associated with considerable mortality. Clinical studies have identified several genes implicated in the pathogenesis of craniosynostosis syndromes with useful insights into the underlying molecular signaling events that determine suture fate. In this review, we exploit the intracellular signal transduction pathways implicated in suture pathobiology, in an attempt to identify key signaling molecules for therapeutic targeting