Proximate mechanisms involved in the formation of Secondary Osteon Morphotypes

2016 ◽  
Vol 25 (02) ◽  
pp. 101-112 ◽  
Author(s):  
M. S. Doutré ◽  
D. J. Weaver ◽  
J. G. Skedros
Keyword(s):  
Extracellular Matrix ◽  
Self Assembly ◽  
Primary Cilia ◽  
Regional Variations ◽  
Proximate Mechanisms ◽  
And Migration ◽  
Blast Alignment ◽  
Cellular Control

SummaryProximate mechanisms involved in forming extracellular matrix (ECM) variations within and between bones are not yet clear. Deficiencies in the collective understanding of details required to illuminate the process that forms a highly ordered ECM are exposed when considering that there is still significant debate as to the importance of cellular control in the assembly of the ECM vs. the observation of collagen fibrillar “self-assembly” (i. e., occurring devoid of cells). We examined data and opinions with respect to possible mechanisms involved in the formation of distinctly different ECM patterns of secondary osteon morphotypes (SOMs). Important considerations include: (1) stretch within the osteoid during fibrillogenesis, (2) various mechanotransduction mechanisms, and (3) whether or not the formation of regional variations in osteonal ECMs requires osteo blast alignment and/or rotation and migration. We propose that primary cilia of osteoblasts and osteocytes have an important role in their perception of variant-related (vectorial) stimuli, which is deemed essential in the genesis of distinctive and mechanically relevant ECM patterns of SOMs.

scholarly journals Mast Cell-Derived SAMD14 is a Novel Regulator of the Human Prostate Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1237
Author(s):  
Linda K. H. Teng ◽  
Brooke A. Pereira ◽  
Shivakumar Keerthikumar ◽  
Cheng Huang ◽  
Birunthi Niranjan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Suppressor Gene ◽  
Prostate Tumor ◽  
Human Prostate ◽  
Proteomic Profiling ◽  
Putative Tumor Suppressor Gene ◽  
Invasion And Migration ◽  
And Migration

Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

scholarly journals Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 361
Author(s):  
Han-Yu Wang ◽  
Chun-Hsiang Lin ◽  
Yi-Ru Shen ◽  
Ting-Yu Chen ◽  
Chia-Yih Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Primary Cilia ◽  
Cell Growth And Migration ◽  
Filament Dynamics ◽  
Gtp Binding ◽  
Cilia Formation ◽  
And Migration ◽  
Septin Filament ◽  
Kinase A

Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among the septins, septin7 (SEPT7) is an important component of all septin filaments. Here we show that protein kinase A (PKA) phosphorylates SEPT7 at Thr197, thus disrupting septin filament dynamics and ciliogenesis. The Thr197 residue of SEPT7, a PKA phosphorylating site, was conserved among different species. Treatment with cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation, followed by disruption of septin filament formation. Constitutive phosphorylation of SEPT7 at Thr197 reduced SEPT7‒SEPT7 interaction, but did not affect SEPT7‒SEPT6‒SEPT2 or SEPT4 interaction. Moreover, we noted that SEPT7 interacted with PKACA2 via its GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.

scholarly journals Nanostructural self-assembly of iridescent feather barbules through depletion attraction of melanosomes during keratinization

2011 ◽  
Vol 9 (69) ◽  
pp. 734-743 ◽  
Author(s):  
Rafael Maia ◽  
Regina H. F. Macedo ◽  
Matthew D. Shawkey
Keyword(s):  
Self Assembly ◽  
Light And Electron Microscopy ◽  
Single Layer ◽  
Metabolic Cost ◽  
Condition Dependence ◽  
Developmental Pathway ◽  
Ordered Arrays ◽  
Cellular Control ◽  
Ornamental Traits ◽  
Nanostructural Organization

Avian plumage colours are model traits in understanding the evolution of sexually selected ornamental traits. Paradoxically, iridescent structural colours, probably the most dazzling of these traits, remain the most poorly understood. Though some data suggest that expression of bright iridescent plumage colours produced by highly ordered arrays of melanosomes and keratin is condition-dependent, almost nothing is known of their ontogeny and thus of any developmental mechanisms that may be susceptible to perturbation. Here, we use light and electron microscopy to compare the ontogeny of iridescent male and non-iridescent female feathers in blue-black grassquits. Feather barbules of males contain a single layer of melanosomes bounded by a thin layer of keratin-producing blue iridescent colour, while those of females contain disorganized melanosomes and no outer layer. We found that nanostructural organization of male barbules occurs late in development, following death of the barbule cell, and is thus unlikely to be under direct cellular control, contrary to previous suggestions. Rather, organization appears to be caused by entropically driven self-assembly through depletion attraction forces that pin melanosomes to the edge of barbule cells and to one another. These forces are probably stronger in developing barbules of males than of females because their melanosomes are (i) larger, (ii) more densely packed, and (iii) more homogeneously distributed owing to the more consistent shape of barbules during keratinization. These data provide the first proposed developmental pathway for iridescent plumage colours, and suggest that any condition dependence of iridescent barbules is likely driven by factors other than direct metabolic cost.

scholarly journals The Extracellular Matrix Glycoprotein Tenascin C and Adult Neurogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Milena Tucić ◽  
Vera Stamenković ◽  
Pavle Andjus
Keyword(s):  
Extracellular Matrix ◽  
Adult Neurogenesis ◽  
Specific Reference ◽  
Neuron Development ◽  
Regulatory Pathways ◽  
Tenascin C ◽  
Extracellular Matrix Components ◽  
Adult Hippocampus ◽  
And Migration ◽  
Regenerative Therapies

Tenascin C (TnC) is a glycoprotein highly expressed in the extracellular matrix (ECM) during development and in the adult central nervous system (CNS) in regions of active neurogenesis, where neuron development is a tightly regulated process orchestrated by extracellular matrix components. In addition, newborn cells also communicate with glial cells, astrocytes and microglia, indicating the importance of signal integration in adult neurogenesis. Although TnC has been recognized as an important molecule in the regulation of cell proliferation and migration, complete regulatory pathways still need to be elucidated. In this review we discuss the formation of new neurons in the adult hippocampus and the olfactory system with specific reference to TnC and its regulating functions in this process. Better understanding of the ECM signaling in the niche of the CNS will have significant implications for regenerative therapies.

scholarly journals Extracellular matrix derived peptides and mesenchymal stem cell motility

2021 ◽  
Author(s):  
◽  
Sandi Grainne Dempsey
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Motility ◽  
Cell Attachment ◽  
Mass Spectrometry Analysis ◽  
And Migration ◽  
Proliferation And Migration

<p>Biomaterials derived from decellularised extracellular matrices have shown promise as tools in tissue regeneration and wound healing. Such materials display biocompatibility as well as inherent bioactivity, promoting constructive remodelling in healing tissues. In this study, the bioactivity of ovine forestomach matrix (a decellularised extracellular matrix biomaterial) is assessed based on its ability to affect the proliferation and migration of wound healing cells.  This material supported cell attachment and proliferation, but did not allow cell infiltration in vitro. Enzymatic digestion of the material rendered soluble components that were able to induce proliferation and migration of some cell types. Cell-mediated processing of the material generated a protein or proteins with chemotactic activity for mesenchymal stem cells in vitro. Mass spectrometry analysis indicated the bioactive component consisted of the proteoglycan decorin, or fragments thereof. Decorin has not previously been shown to induce mesenchymal stem cell motility, and these findings may add to what is known about decorin and its role in constructive remodelling. Furthermore, this cell-mediated approach for ECM breakdown could lead to the discovery of other bioactive peptides involved in ECM remodelling and wound healing.</p>

scholarly journals Loss of Kallmann syndrome-associated gene WDR11 disrupts primordial germ cell development by affecting canonical and non-canonical Hedgehog signalling

2020 ◽  
Author(s):  
Jiyoung Lee ◽  
Yeonjoo Kim ◽  
Paris Ataliotis ◽  
Hyung-Goo Kim ◽  
Dae-Won Kim ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Primary Cilia ◽  
Primordial Germ Cell ◽  
Kallmann Syndrome ◽  
Loss Of Function ◽  
Downstream Effectors ◽  
Cell Components ◽  
Underlying Mechanisms ◽  
And Migration

ABSTRACTMutations of WDR11 are associated with Kallmann syndrome (KS) and congenital hypogonadotrophic hypogonadism (CHH), typically caused by defective functions of gonadotrophin-releasing hormone (GnRH) neurones in the brain. We previously reported that Wdr11 knockout mice show profound infertility with significantly fewer germ cells present in the gonads. To understand the underlying mechanisms mediated by WDR11 in these processes, we investigated the effects of Wdr11 deletion on primordial germ cell (PGC) development. Using live-tracking of PGCs and primary co-cultures of genital ridges (GR), we demonstrated that Wdr11-deficient embryos contained reduced numbers of PGCs which had delayed migration due to significantly decreased proliferation and motility. We found primary cilia-dependent canonical Hedgehog (Hh) signalling was required for proliferation of the somatic mesenchymal cells of GR, while primary cilia-independent non-canonical Hh signalling mediated by Ptch2/Gas1 and downstream effectors Src and Creb was required for PGC proliferation and migration, which was disrupted by the loss of function mutations of WDR11. Therefore, canonical and non-canonical Hh signalling are differentially involved in the development of somatic and germ cell components of the gonads, and WDR11 is required for both of these pathways operating in parallel in GR and PGCs, respectively, during normal PGC development. Our study provides a mechanistic link between the development of GnRH neurones and germ cells mediated by WDR11, which may underlie some cases of KS/CHH and ciliopathies.

scholarly journals Dynamic expression of MMP28 during cranial morphogenesis

2020 ◽  
Vol 375 (1809) ◽  
pp. 20190559 ◽  
Author(s):  
Nadege Gouignard ◽  
Eric Theveneau ◽  
Jean-Pierre Saint-Jeannet
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Neural Crest ◽  
Large Family ◽  
Tail Bud ◽  
Dynamic Expression ◽  
The Family ◽  
Extracellular Matrix Remodelling ◽  
And Migration ◽  
Human And Mouse

Matrix metalloproteinases (MMPs) are a large family of proteases comprising 24 members in vertebrates. They are well known for their extracellular matrix remodelling activity. MMP28 is the latest member of the family to be discovered. It is a secreted MMP involved in wound healing, immune system maturation, cell survival and migration. MMP28 is also expressed during embryogenesis in human and mouse. Here, we describe the detailed expression profile of MMP28 in Xenopus laevis embryos. We show that MMP28 is expressed maternally and accumulates at neurula and tail bud stages specifically in the cranial placode territories adjacent to migrating neural crest cells. As a secreted MMP, MMP28 may be required in neural crest–placode interactions. This article is part of a discussion meeting issue ‘Contemporary morphogenesis’.

scholarly journals AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoling Liu ◽  
Chenyu Wang ◽  
Qing Yang ◽  
Yue Yuan ◽  
Yunjian Sheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Biological Function ◽  
Cell Metabolism ◽  
Hub Genes ◽  
Invasion And Migration ◽  
And Migration

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis.Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC.Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs.Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

scholarly journals Islet vascularization is regulated by primary endothelial cilia via VEGF-A-dependent signaling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yan Xiong ◽  
M Julia Scerbo ◽  
Anett Seelig ◽  
Francesco Volta ◽  
Nils O'Brien ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Primary Cilia ◽  
Capillary Density ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Downstream Signaling ◽  
Vegfr2 Signaling ◽  
And Migration ◽  
Endothelial Growth Factor

Islet vascularization is essential for intact islet function and glucose homeostasis. We have previously shown that primary cilia directly regulate insulin secretion. However, it remains unclear whether they are also implicated in islet vascularization. At eight weeks, murine Bbs4-/-islets show significantly lower intra-islet capillary density with enlarged diameters. Transplanted Bbs4-/- islets exhibit delayed re-vascularization and reduced vascular fenestration after engraftment, partially impairing vascular permeability and glucose delivery to β-cells. We identified primary cilia on endothelial cells as the underlying cause of this regulation, via the vascular endothelial growth factor-A (VEGF-A)/VEGF receptor 2 (VEGFR2) pathway. In vitro silencing of ciliary genes in endothelial cells disrupts VEGF-A/VEGFR2 internalization and downstream signaling. Consequently, key features of angiogenesis including proliferation and migration are attenuated in human BBS4 silenced endothelial cells. We conclude that endothelial cell primary cilia regulate islet vascularization and vascular barrier function via the VEGF-A/VEGFR2 signaling pathway.

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