Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

Pivotal Role of the Granularity Uniformity of the WO3 Film Electrode upon the Cyclic Stability during Cation Insertion/Extraction.

Delicate design and precise manipulation of electrode morphology has always been crucial in electrochemistry. Generally, porous morphology has been preferred due to the fast kinetic transport characteristics of cations. Nevertheless, more refined design details such as the granularity uniformity that usually goes along with the porosity regulation of film electrodes should be taken into consideration, especially in long-term cation insertion and extraction. Here, inorganic electrochromism as a special member of the electrochemical family and WO3 films as the most mature electrochromic electrode material were chosen as the research background. Two kinds of WO3 films were prepared by magnetron sputtering, one with a relatively loose morphology accompanied by nonuniform granularity and one with a compact morphology along with uniform particle size distribution, respectively. Electrochemical performances and cyclic stability of the two film electrodes were then traced and systematically compared. In the beginning, except for faster kinetic transport characters of the 50 W-deposited WO3 film, the two electrodes showed equivalent optical and electrochemical performances. However, after 5000 CV cycles, the 50 W-deposited WO3 film electrode cracked seriously. Strong stress distribution centered among boundaries of the nonuniform particle clusters together with the weak bonding among particles induced the mechanical damage. This discovery provides a more solid background for further delicate film electrode design.

The Homeostasis of Cartilage Matrix Remodeling and the Regulation of Volume-Sensitive Ion Channel.

Degenerative joint diseases of the hips and knees are common and are accompanied by severe pain and movement disorders. At the microscopic level, the main characteristics of osteoarthritis are the continuous destruction and degeneration of cartilage, increased cartilage extracellular matrix catabolism, decreased anabolism, increased synovial fluid, and decreased osmotic pressure. Cell volume stability is mainly regulated by ion channels, many of which are expressed in chondrocytes. These ion channels are closely related to pain regulation, volume regulation, the inflammatory response, cell proliferation, apoptosis, and cell differentiation. In this review, we focus on the important role of volume control-related ion channels in cartilage matrix remodeling and summarize current views. In addition, the potential mechanism of the volume-sensitive anion channel LRRC8A in the early occurrence of osteoarthritis is discussed.

Chloride Channel and Inflammation-Mediated Pathogenesis of Osteoarthritis.

Articular cartilage allows the human body to buffer and absorb stress during normal exercise. It is mainly composed of cartilage cells and the extracellular matrix and is surrounded by the extracellular microenvironment formed by synovial fluid and various factors in it. Studies have shown that chondrocytes are the metabolic center of articular cartilage. Under physiological conditions, the extracellular matrix is in a dynamic balance of anabolism and catabolism, and various factors and physical and chemical conditions in the extracellular microenvironment are also in a steady state. This homeostasis depends on the normal function of proteins represented by various ion channels on chondrocytes. In mammalian chondrocyte species, ion channels are mainly divided into two categories: cation channels and anion channels. Anion channels such as chloride channels have become hot research topics in recent years. These channels play an extremely important role in various physiological processes. Recently, a growing body of evidence has shown that many pathological processes, abnormal concentration of mechanical stress and chloride channel dysfunction in articular cartilage lead to microenvironment disorders, matrix and bone metabolism imbalances, which cause partial aseptic inflammation. These pathological processes initiate extracellular matrix degradation, abnormal chondrocyte death, hyperplasia of inflammatory synovium and bony. Osteoarthritis (OA) is a common clinical disease in orthopedics. Its typical manifestations are joint inflammation and pain caused by articular cartilage degeneration, but its pathogenesis has not been fully elucidated. Focusing on the physiological functions and pathological changes of chloride channels and pathophysiology of aseptic inflammation furthers the understanding of OA pathogenesis and provides possible targets for subsequent medication development.

Crosstalk between immune cells and bone cells or chondrocytes.

The term "osteoimmunology" was coined to denote the bridge between the immune system and the skeletal system. Osteoimmunology is interdisciplinary, and a full understanding and development of this "bridge" will provide an in-depth understanding of the switch between body health and disease development. B lymphocytes can promote the maturation and differentiation of osteoclasts, and osteoclasts have a negative feedback effect on B lymphocytes. Different subtypes of T lymphocytes regulate osteoclasts in different directions. T lymphocytes have a two-way regulatory effect on osteoblasts, while B lymphocytes have minimal regulatory effects on osteoblasts. In contrast, osteoblasts can promote the differentiation and maturation of T lymphocytes and B lymphocytes. Different immune cells have different effects on chondrocytes; some cooperate with each other, while some antagonize each other. In a healthy adult body, bone resorption and bone formation are in a dynamic balance under the action of multiple mechanisms. In this review, we summarize the interactions and key signaling molecular mechanisms between each type of cell in the immune system and the skeletal system.

Interleukin 1 beta-induced chloride currents are important in osteoarthritis onset: an in vitro study.

Persistent hypotonic and inflammatory conditions in the joint cavity can lead to the loss of cartilage matrix and cell death, which are the important mechanisms of osteoarthritis (OA) onset. Previous studies have confirmed that the existence of a hypotonic environment is a red flag for inflammation, as hypotonic environment induces the opening of the chloride channel of the cell and promotes chloride ion efflux, which prompts the cell volume to increase. Chloride channels play an important role in the regulation of mineralization and chondrocyte death. Here, we reported that OA chondrocytes showed a significant increase of cell death rate and the imbalance of cartilage matrix catabolism. We found that the distribution of skeleton protein F-actin was disordered. In addition, the volume-sensitive chloride current of OA chondrocytes decreased significantly with the increase of the expression levels of inflammation-related proteins caspase-1, caspase-3, and NLRP3. Moreover, interleukin-1ß (IL-1ß) showed a potential to activate the chloride current of normal chondrocytes. These results indicate that IL-1ß-induced chloride channel opening in chondrocytes may be closely related to the occurrence of OA. This chloride channel opening process may therefore be a potential target for the treatment of OA.

Biodegradation Assessment of Poly (Lactic Acid) Filled with Functionalized Titania Nanoparticles (PLA/TiO2) under Compost Conditions.

This paper presents a biodegradation study conducted for 90 days under standardized controlled composting conditions of poly (lactic acid) (PLA) filled with functionalized anatase-titania nanofiller (PLA/TiO2 nanocomposites). The surface morphology, thermal properties, percentage of biodegradation, and molecular weight changes at different incubation times were evaluated via visual inspection, scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) by taking degraded samples from compost at the end of target biodegradation time interval. The rapid increase of crystallinity indicated that the PLA and PLA/TiO2 nanocomposites had heterogeneous degradation mechanisms under controlled composting conditions. The biodegradation rate of PLA/TiO2 nanocomposites was higher than that of pure PLA because water molecules easily penetrated the nanocomposites. The dispersion of the nanoparticles in the PLA/TiO2 nanocomposites affected the biodegradation rate of PLA. Moreover, the biodegradation of PLA could be controlled by adding an amount of dispersed TiO2 nanofillers under controlled composting conditions.