scholarly journals Aberrant subchondral osteoblastic metabolism modifies NaV1.8 for osteoarthritis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jianxi Zhu ◽  
Gehua Zhen ◽  
Senbo An ◽  
Xiao Wang ◽  
Mei Wan ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone ◽  
Degenerative Diseases ◽  
Drg Neurons ◽  
Potential Therapeutic Target ◽  
Prominent Symptom ◽  
Important Player ◽  
Pge2 Receptor ◽  
The Relationship ◽  
Specific Deletion

Pain is the most prominent symptom of osteoarthritis (OA) progression. However, the relationship between pain and OA progression remains largely unknown. Here we report osteoblast secret prostaglandin E2 (PGE2) during aberrant subchondral bone remodeling induces pain and OA progression in mice. Specific deletion of the major PGE2 producing enzyme cyclooxygenase 2 (COX2) in osteoblasts or PGE2 receptor EP4 in peripheral nerve markedly ameliorates OA symptoms. Mechanistically, PGE2 sensitizes dorsal root ganglia (DRG) neurons by modifying the voltage-gated sodium channel NaV1.8, evidenced by that genetically or pharmacologically inhibiting NaV1.8 in DRG neurons can substantially attenuate OA. Moreover, drugs targeting aberrant subchondral bone remodeling also attenuates OA through rebalancing PGE2 production and NaV1.8 modification. Thus, aberrant subchondral remodeling induced NaV1.8 neuronal modification is an important player in OA and is a potential therapeutic target in multiple skeletal degenerative diseases.

XIST: A Meaningful Long Noncoding RNA in NSCLC Process

2020 ◽  
Vol 26 ◽  
Author(s):  
Yujie Shen ◽  
Yexiang Lin ◽  
Kai Liu ◽  
Jinlan Chen ◽  
Juanjuan Zhong ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Biological Functions ◽  
Potential Therapeutic Target ◽  
Considerable Evidence ◽  
Lncrna Xist ◽  
Nsclc Patients ◽  
The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

Early inhibition of subchondral bone remodeling slows load‐induced post‐traumatic osteoarthritis development in mice

2021 ◽  
Author(s):  
Sophia N. Ziemian ◽  
Ana Witkowski ◽  
Timothy M Wright ◽  
Miguel Otero ◽  
Marjolein C. H. Meulen
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone ◽  
Post Traumatic ◽  
Early Inhibition

scholarly journals The relationship of humeroscapular periarthrosis and the spine degenerative diseases

2015 ◽  
pp. 50-54
Author(s):  
A.A. Lutsik ◽  
◽  
V.M. Prokhorenko ◽  
I.S. Tregub ◽  
G.Iu. Bondarenko ◽  
...  
Keyword(s):  
Degenerative Diseases ◽  
Relationship Of ◽  
The Relationship

scholarly journals Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaobo Zhu ◽  
Yau Tsz Chan ◽  
Patrick S. H. Yung ◽  
Rocky S. Tuan ◽  
Yangzi Jiang
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Bone Remodeling ◽  
Molecular Mechanism ◽  
Subchondral Bone ◽  
Therapeutic Target ◽  
Therapeutic Targets ◽  
Regenerative Therapies

There is emerging awareness that subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). This review presents recent investigations on the cellular and molecular mechanism of subchondral bone remodeling, and summarizes the current interventions and potential therapeutic targets related to OA subchondral bone remodeling. The first part of this review covers key cells and molecular mediators involved in subchondral bone remodeling (osteoclasts, osteoblasts, osteocytes, bone extracellular matrix, vascularization, nerve innervation, and related signaling pathways). The second part of this review describes candidate treatments for OA subchondral bone remodeling, including the use of bone-acting reagents and the application of regenerative therapies. Currently available clinical OA therapies and known responses in subchondral bone remodeling are summarized as a basis for the investigation of potential therapeutic mediators.

scholarly journals CHD8 regulates gut epithelial cell function and affects autism-related behaviours through the gut-brain axis

2021 ◽  
Author(s):  
Ipsita Chaterjee ◽  
Dmitriy Getselter ◽  
Nasreen Ghaneem ◽  
Shai Bel ◽  
Evan Elliott
Keyword(s):  
Epithelial Cells ◽  
Cell Function ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Direct Role ◽  
Tuft Cells ◽  
Core Symptoms ◽  
The Relationship ◽  
Specific Deletion

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by early onset deficits in social behavior and repetitive behavior. Chromodomain helicase DNA binding protein (CHD8) is one of the genes with the strongest association to autism. Alongside with the core symptoms of ASD, individuals with ASD are reported to have gastrointestinal (GI) problems, and a majority of individuals with CHD8 mutations display GI problems. However, the relationship between autism related genes, such as CHD8, gastrointestinal function, and autism related behaviours are yet very unclear. In the current study, we found that mice haploinsufficient for CHD8 have leaky gut, a dysregulated transcriptome in gut epithelial cells, decreased gut tuft cells and goblet cells, and an increase in microbial load. Specific deletion of CHD8 in gut epithelial cells induced an increase in anxiety-related behaviours in, a phenotype that is often observed in autism and full body knockdown of CHD8, in addition to decreased tuft cells. In addition, antibiotic treatment of CHD8 haploinsufficient mice attenuates sociability deficits. Therefore, the current study determines a pathway for autism-related GI deficits, and how these deficits may play a direct role in the development of autism-related behaviours.

scholarly journals Dihydroartemisinin attenuates osteoarthritis by inhibiting abnormal bone remodeling and angiogenesis in subchondral bone

2021 ◽  
Vol 47 (3) ◽  
Author(s):  
Long Ma ◽  
Xin Zhao ◽  
Yibin Liu ◽  
Jiang Wu ◽  
Xiaochun Yang ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone

Synaptic interactions between mammalian central neurons in cell culture. II. Quantal Analysis of EPSPs

1983 ◽  
Vol 49 (6) ◽  
pp. 1442-1458 ◽  
Author(s):  
P. G. Nelson ◽  
K. C. Marshall ◽  
R. Y. Pun ◽  
C. N. Christian ◽  
W. H. Sheriff ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Culture Medium ◽  
Ion Concentration ◽  
Release Mechanism ◽  
Drg Neurons ◽  
Release Process ◽  
Central Neurons ◽  
Synaptic Interactions ◽  
Presynaptic Release ◽  
The Relationship

The presynaptic release mechanism involved in excitatory synaptic connections between neurons in cell cultures of fetal mouse spinal cord were studied by statistical analysis of intracellularly recorded postsynaptic responses. Quantal parameters were determined for the EPSPs evoked in spinal cord (SC) neurons by stimulation of either other SC or dorsal root ganglion (DRG) neurons. Transmitter release was manipulated by varying the Ca2+ and Mg2+ content of the culture medium. The release process was represented better by binomial than by Poisson statistics. A method was derived for obtaining the probability of release and the number of release elements. The quantal content and the number of release elements were substantially higher for the SC-SC connection than for the DRG-SC connection. This was partially compensated for by a larger quantal amplitude for the DRG-SC connection. There was some indication that the probability of release was higher for the SC-SC connection. The relationship between transmitter output and effective external Ca2+ ion concentration was approximately linear.

scholarly journals The Role of Tumor-Infiltrating B Cells in Tumor Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Fei Guo ◽  
Jiu Wei Cui
Keyword(s):  
T Cells ◽  
B Cells ◽  
Tumor Immunity ◽  
Therapeutic Target ◽  
Tumor Biomarker ◽  
Potential Therapeutic Target ◽  
Tumor Inhibition ◽  
Tumor Tissues ◽  
The Relationship

Earlier studies on elucidating the role of lymphocytes in tumor immunity predominantly focused on T cells. However, the role of B cells in tumor immunity has increasingly received better attention in recent studies. The B cells that infiltrate tumor tissues are called tumor-infiltrating B cells (TIBs). It is found that TIBs play a multifaceted dual role in regulating tumor immunity rather than just tumor inhibition or promotion. In this article, latest research advances focusing on the relationship between TIBs and tumor complexity are reviewed, and light is shed on some novel ideas for exploiting TIBs as a possible tumor biomarker and potential therapeutic target against tumors.

scholarly journals Noggin Inhibits IL-1β and BMP-2 Expression, and Attenuates Cartilage Degeneration and Subchondral Bone Destruction in Experimental Osteoarthritis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 927 ◽  
Author(s):  
Szu-Yu Chien ◽  
Chun-Hao Tsai ◽  
Shan-Chi Liu ◽  
Chien-Chung Huang ◽  
Tzu-Hung Lin ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathways ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Bone Destruction ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Mitogen Activated Protein Kinase ◽  
Bone Morphogenetic Protein 2 ◽  
Joint Disease

Osteoarthritis (OA) is a chronic inflammatory and progressive joint disease that results in cartilage degradation and subchondral bone remodeling. The proinflammatory cytokine interleukin 1 beta (IL-1β) is abundantly expressed in OA and plays a crucial role in cartilage remodeling, although its role in the activity of chondrocytes in cartilage and subchondral remodeling remains unclear. In this study, stimulating chondrogenic ATDC5 cells with IL-1β increased the levels of bone morphogenetic protein 2 (BMP-2), promoted articular cartilage degradation, and enhanced structural remodeling. Immunohistochemistry staining and microcomputed tomography imaging of the subchondral trabecular bone region in the experimental OA rat model revealed that the OA disease promotes levels of IL-1β, BMP-2, and matrix metalloproteinase 13 (MMP-13) expression in the articular cartilage and enhances subchondral bone remodeling. The intra-articular injection of Noggin protein (a BMP-2 inhibitor) attenuated subchondral bone remodeling and disease progression in OA rats. We also found that IL-1β increased BMP-2 expression by activating the mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK), and specificity protein 1 (Sp1) signaling pathways. We conclude that IL-1β promotes BMP-2 expression in chondrocytes via the MEK/ERK/Sp1 signaling pathways. The administration of Noggin protein reduces the expression of IL-1β and BMP-2, which prevents cartilage degeneration and OA development.

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