scholarly journals Correlation between LncRNA Profiles in the Blood Clot Formed on Nano-Scaled Implant Surfaces and Osseointegration

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 674
Author(s):  
Long Bai ◽  
Peiru Chen ◽  
Bin Tang ◽  
Ruiqiang Hang ◽  
Yin Xiao
Keyword(s):  
Signaling Pathways ◽  
Cellular Response ◽  
De Novo ◽  
Blood Clot ◽  
Cell Metabolism ◽  
Osteoclast Differentiation ◽  
Vegf Signaling ◽  
Titania Nanotube Arrays ◽  
Pathway Analyses ◽  
Clot Structure

Implant surfaces with a nanoscaled pattern can dominate the blood coagulation process resulting in a defined clot structure and its degradation behavior, which in turn influence cellular response and the early phase of osseointegration. Long non-coding (Lnc) RNAs are known to regulate many biological processes in the skeletal system; however, the link between the LncRNA derived from the cells within the clot and osseointegration has not been investigated to date. Hence, the sequence analysis of LncRNAs expressed within the clot formed on titania nanotube arrays (TNAs) with distinct nano-scaled diameters (TNA 15 of 15 nm, TNA 60 of 60 nm, TNA 120 of 120 nm) on titanium surfaces was profiled for the first time. LncRNA LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 were identified as the pivotal players in the early formed clot on the nano-scaled surfaces. Further bioinformatic prediction results were used to generate co-expression networks of LncRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that distinct nano-scaled surfaces could regulate the biological functions of target mRNAs in the clot. LOC103346307, LOC108175175, and LOC108176660 upregulated mRNAs related to cell metabolism and Wnt, TGF-beta, and VEGF signaling pathways in TNA 15 compared with P-Ti, TNA 60, and TNA 120, respectively, whereas LOC103352121, LOC103348180, and LOC108176465 downregulated mRNAs related to bone resorption and inflammation through negatively regulating osteoclast differentiation, TNF, and NF-kappa signaling pathways. The results indicated that surface nano-scaled characteristics can significantly influence the clot-derived LncRNAs expression profile, which affects osseointegration through multiple signaling pathways of the targeted mRNAs, thus paving a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and de novo bone formation.

Identification of Key Genes and Pathways in Osteoarthritis via Bioinformatic Tools: An Updated Analysis

Cartilage ◽  
2021 ◽  
pp. 194760352110089
Author(s):  
Yijian Zhang ◽  
Tianfeng Zhu ◽  
Fan He ◽  
Angela Carley Chen ◽  
Huilin Yang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cellular Response ◽  
Osteoclast Differentiation ◽  
Molecular Function ◽  
Biological Processes ◽  
R Software ◽  
Bioinformatic Tools ◽  
Go Enrichment ◽  
Upregulated Genes ◽  
Go Terms

Objective Osteoarthritis (OA) is a severe and common degenerative disease; however, the exact pathology of OA is undefined. Our study is designed to investigate the underlying molecular mechanism of OA with bioinformatic tools. Design Three updated GEO datasets: GSE55235, GSE55457, and GSE82107 were selected for data analyzing. R software was utilized to screen and confirm the candidate differentially expressed genes in the development of OA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway were performed to identify the enriched GO terms and signaling pathways. Protein and protein interaction (PPI) models were built to observe the connected relationship among each potential protein. Results A total of 113 upregulated genes and 161 downregulated genes were found by integrating 3 datasets. GO enrichment indicated that cell differentiation, cellular response to starvation, and negative regulation of phosphorylation were important biological processes. KEGG enrichment indicated that FoxO, IL-17 signaling pathways, and osteoclast differentiation mainly participated in the progression of OA. Combining the molecular function and PPI results, ubiquitylation was identified as a pivotal bioactive reaction involved in OA. Conclusion Our study provided updated candidate genes and pathways of OA, which may benefit further research and treatment for OA.

scholarly journals Repetitive in vivo manual loading of the spine elicits cellular responses in porcine annuli fibrosi

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248104
Author(s):  
John Robert Matyas ◽  
Claudia Klein ◽  
Dragana Ponjevic ◽  
Neil A. Duncan ◽  
Gregory N. Kawchuk
Keyword(s):  
Intervertebral Disc ◽  
Manual Therapy ◽  
Cellular Response ◽  
Cell Metabolism ◽  
Low Frequency ◽  
Intervertebral Discs ◽  
Disc Cell ◽  
Therapy Interventions ◽  
Pathway Analyses

Back pain and intervertebral disc degeneration are prevalent, costly, and widely treated by manual therapies, yet the underlying causes of these diseases are indeterminate as are the scientific bases for such treatments. The present studies characterize the effects of repetitive in vivo manual loads on porcine intervertebral disc cell metabolism using RNA deep sequencing. A single session of repetitive manual loading applied to the lumbar spine induced both up- and down-regulation of a variety of genes transcribed by cells in the ventral annuli fibrosi. The effect of manual therapy at the level of loading was greater than at a level distant to the applied load. Gene ontology and molecular pathway analyses categorized biological, molecular, and cellular functions influenced by repetitive manual loading, with over-representation of membrane, transmembrane, and pericellular activities. Weighted Gene Co-expression Network Analysis discerned enrichment in genes in pathways of inflammation and skeletogenesis. The present studies support previous findings of intervertebral disc cell mechanotransduction, and are the first to report comprehensively on the repertoire of gene targets influenced by mechanical loads associated with manual therapy interventions. The present study defines the cellular response of repeated, low-amplitude loads on normal healthy annuli fibrosi and lays the foundation for future work defining how healthy and diseased intervertebral discs respond to single or low-frequency manual loads typical of those applied clinically.

scholarly journals The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 855
Author(s):  
Paola Serrano Martinez ◽  
Lorena Giuranno ◽  
Marc Vooijs ◽  
Robert P. Coppes
Keyword(s):  
Signaling Pathways ◽  
Progenitor Cells ◽  
Tissue Regeneration ◽  
Normal Tissue ◽  
Cellular Response ◽  
Adult Tissue ◽  
Tissue Specific ◽  
Radiation Induced

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

scholarly journals Inhibitory Effect of LGS and ODE Isolated from the Twigs of Syringa oblata subsp. dilatata on RANKL-Induced Osteoclastogenesis in Macrophage Cells

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1779
Author(s):  
Ga-Ram Kim ◽  
Eun-Nam Kim ◽  
Kyoung Jin Park ◽  
Ki Hyun Kim ◽  
Gil-Saeng Jeong
Keyword(s):  
Protein Kinase ◽  
Bone Resorption ◽  
Signaling Pathways ◽  
Natural Product ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Pivotal Role ◽  
Nuclear Factor ◽  
Bone Homeostasis ◽  
Nuclear Factor Kappa

Osteoblasts and osteoclasts play a pivotal role in maintaining bone homeostasis, of which excessive bone resorption by osteoclasts can cause osteoporosis and various bone diseases. However, current osteoporosis treatments have many side effects, and research on new treatments that can replace these treatments is ongoing. Therefore, in this study, the roles of ligustroside (LGS) and oleoside dimethylester (ODE), a natural product-derived compound isolated from Syringa oblata subsp. dilatata as a novel, natural product-derived osteoporosis treatments were investigated. In the results of this study, LGS and ODE inhibited the differentiation of receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced RAW264.7 cells into osteoclasts without cytotoxicity, and down-regulated the activity of TRAP, a specific biomarker of osteoclasts. In addition, it inhibited bone resorption and actin ring formation, which are important functions and features of osteoclasts. Also, the effects of LGS and ODE on the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and phosphoinositide 3-kinases (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathways that play important roles in osteoclast differentiation were evaluated. In the results, LGS and ODE downregulated the phosphorylation of RANKL-induced MAPK and PI3K/Akt/mTOR proteins in a concentration-dependent manner, translocation of NF-κB into the nucleus was inhibited. As a result, the compounds LGS and ODE isolated from S. oblate subsp. dilatata effectively regulated the differentiation of RANKL-induced osteoclasts and inhibited the phosphorylation of signaling pathways that play a pivotal role in osteoclast differentiation. Therefore, these results suggest the possibility of LGS and ODE as new natural product treatments for bone diseases caused by excessive osteoclasts.

scholarly journals Augmenting Signaling Pathway Reconstructions

2020 ◽  
Author(s):  
Tobias Rubel ◽  
Anna Ritz
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Protein Interactions ◽  
Cellular Response ◽  
Ground Truth ◽  
Protein Interaction Data ◽  
Reconstruction Method ◽  
Reconstruction Algorithms ◽  
Molecular Systems ◽  
Pathway Reconstruction

AbstractSignaling pathways drive cellular response, and understanding such pathways is fundamental to molecular systems biology. A mounting volume of experimental protein interaction data has motivated the development of algorithms to computationally reconstruct signaling pathways. However, existing methods suffer from low recall in recovering protein interactions in ground truth pathways, limiting our confidence in any new predictions for experimental validation. We present the Pathway Reconstruction AUGmenter (PRAUG), a higher-order function for producing high-quality pathway reconstruction algorithms. PRAUG modifies any existing pathway reconstruction method, resulting in augmented algorithms that outperform their un-augmented counterparts for six different algorithms across twenty-nine diverse signaling pathways. The algorithms produced by PRAUG collectively reveal potential new proteins and interactions involved in the Wnt and Notch signaling pathways. PRAUG offers a valuable framework for signaling pathway prediction and discovery.

Rapid generation of Hybrid Biochemical/Mechanical Cues in Heterogeneous Droplets for High-Throughput Screening of Cellular Response

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Xing Zhao ◽  
Gaozhi Ou ◽  
Mengcheng Lei ◽  
Yang Zhang ◽  
Lina Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cellular Response ◽  
Wide Range ◽  
Rapid Generation ◽  
P Cells

Cells in native microenvironment are subjected to varying combinations of biochemical cues and mechanical cues in a wide range. Despite many signaling pathways have been found to be responsive for...

Multi-Omics Analysis to Reveal Disorders of Cell Metabolism and Integrin Signaling Pathways induced by PM2.5

2021 ◽  
pp. 127573
Author(s):  
Xiaoyao Song ◽  
Jianhui Liu ◽  
Ningbo Geng ◽  
Yichu Shan ◽  
Baoqin Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Metabolism ◽  
Integrin Signaling ◽  
Omics Analysis

Abstract 13695: Paracrine-mediated Rejuvenation of Aged Mesenchymal Stem Cells Involves Broad Transcriptional Modulation of Angiogenic Factors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
George Hung ◽  
Andreas S Barth ◽  
Peter V Johnston ◽  
Gary Gerstenblith
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Tissue Repair ◽  
Target Enrichment ◽  
Aged Patients ◽  
Vegf Signaling ◽  
Marrow Mesenchymal Stem Cells ◽  
C57bl Mice ◽  
Transcriptional Modulation

Introduction: Angiogenesis induced by bone marrow mesenchymal stem cells (MSCs) obtained from aged mice is inferior to those obtained from young mice, but is improved following exposure to conditioned media (CM) from young MSCs. To define alterations in gene expression and signaling pathways underlying the observed angiogenic improvement, we characterized differences in cellular mRNA expression between “non-rejuvenated” and “rejuvenated” (exposed to CM from young MSCs) old MSCs. Methods: Replicates of 105 MSCs isolated from old (18-24 months) C57BL mice (n=6) were cultured separately, or in co-culture with MSCs from young (4-6 weeks, n=6) mice using 0.4μm Transwell plates that allow transfer of soluble factors, but not of cells. After 7d in culture, mRNA from old and rejuvenated MSCs was isolated and sequenced. Analysis was performed using open source Galaxy pipeline. Transcription factor (TF) and miRNA target enrichment analyses were performed using ChEA3 and MIENTURNET. Results: Of the 529 unique transcripts involved in angiogenesis (GO-ID 0001525), 98 differentially expressed transcripts (Bonferroni p < 0.0001) were identified. The rejuvenated MSCs showed significantly increased expression of 39 genes. The majority of these involved canonical angiogenic pathways and/or regulation of VEGF: JAK1, LOXL2, KLF4, BMP4, and ADM. Top enriched TFs and miRNAs included EPAS1 and miR-20a, respectively, both directly involved in VEGF signaling, along with SOX18, SNAI1, SOX7, miR-126a, and miR-499 (FDR < 0.05), all of which are known to promote either angiogenesis and/or stemness. Conclusions: Improved angiogenesis by old MSCs exposed to CM from young MSCs is accompanied by significant modulation of angiogenic mediators, crucial in both VEGF and non-VEGF signaling pathways. These changes suggest targets for transcriptional modification to improve angiogenesis and tissue repair in aged patients.

scholarly journals Regenerating the Pulp–Dentine Complex Using Autologous Platelet Concentrates: A Critical Appraisal of the Current Histological Evidence

2020 ◽  
Author(s):  
Amna Riaz ◽  
Furqan A. Shah
Keyword(s):  
De Novo ◽  
Platelet Rich Plasma ◽  
Blood Clot ◽  
Permanent Teeth ◽  
Morphological Evidence ◽  
Wall Thickening ◽  
Platelet Concentrates ◽  
Pulp Tissue ◽  
True Nature ◽  
Autologous Platelet

Background: Autologous platelet concentrates such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) have gained overwhelming popularity in regenerative endodontics. Clinical evidence reveals the lack of a particular advantage of using PRP or PRF over an evoked blood clot in promoting canal wall thickening and/or continued root development in immature necrotic teeth. Moreover, despite stimulating tissue repair and repopulating the root canals of immature and mature permanent teeth, the new vital tissue may not possess the functional activity of the native pulp tissue. Methods: To better understand the origin, nature, and long-term fate of the tissue types found within the pulp space, we critically examine all available histo-/morphological evidence for pulp–dentine complex regeneration using PRP and/or PRF, alone or together with an evoked blood clot, specialised or unspecialised primary cells, and other biomaterials. Results: Histological data from clinical studies is scant. Reportedly, the inner dentinal surface supports cementum-like tissue formation, but this interface likely deviates in structure and function from the native cementodentinal junction. Presence of bone-like tissue within the pulp space is intriguing since de novo osteogenesis requires closely coordinated recruitment and differentiation of osteoprogenitor cells. Compared to untreated necrotic teeth, an evoked blood clot (with/without PRF) improves fracture resistance. Tooth regeneration using PRF and dental bud cells is unreliable and the constituent neoformed tissues are poorly organised. Conclusion: PRP/PRF fail to demonstrate a significant advantage over an induced blood clot, alone. The true nature of neoformed tissues remains poorly characterised while their response to subsequent insult/injury is unexplored.

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