a-3-d-visualization-technique-for-bone-remodeling-suture-expansion

A 3-D Visualization Technique for Bone Remodeling in a Suture Expansion Mouse Model

Craniofacial sutures play a crucial role beyond being fibrous joints connecting craniofacial bones; they also serve as the primary niche for calvarial and ...

Shanghai Jiao Tong University School of Medicine

Shanghai Jiao Tong University

Osteoarthritis (OA) is a common disease for human beings, characterized by severe inflammation, cartilage degradation, and subchondral bone destruction. However, current therapies are limited to relieving pain or joint replacement and no effective treatment methods have been discovered to improve degenerative changes. Currently, a variety of evidences have indicated that aberrant mechanical stimuli is closely associated with articular joint pathogenesis, while the detailed underlying mechanism remains unelucidated. In the present study, we determined to investigate the impact of excessive high fluid shear stress (FSS) on primary chondrocytes and the underlying epigenetic mechanisms.

Aberrant Fluid Shear Stress Contributes to Articular Cartilage Pathogenesis via Epigenetic Regulation of ZBTB20 by H3K4me3.

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.

Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1.

Osteoarthritis (OA) is a common joint disorder worldwide which causes great health and economic burden. However, there remains an unmet goal to develop an effective therapeutic method to prevent or delay OA. Chondrocytes, as the major cells involved in OA progression, may serve as a promising therapeutic target.

Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages.

Orthodontic tooth movement (OTM) has previously been considered an inflammatory process. However, recent studies suggest that exosomes may play an important role in the cellular microenvironment of OTM. microRNAs (miRNAs) are one of the major constituents of exosomes. This study aims to investigate the biological characteristics of miRNAs secreted by exosomes of periodontal ligament stem cells (PDLSCs) due to mechanical forces.

Article	Year
Aberrant Fluid Shear Stress Contributes to Articular Cartilage Pathogenesis via Epigenetic Regulation of ZBTB20 by H3K4me3. Journal of inflammation research\| PubMed ID: 34824542	2021
Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1. International journal of oral science\| PubMed ID: 35831280	2022
Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages. Journal of nanobiotechnology\| PubMed ID: 36329497	2022
Biological characteristics of microRNAs secreted by exosomes of periodontal ligament stem cells due to mechanical force. European journal of orthodontics\| PubMed ID: 37262013	2023

Zhenxia Li

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