COMP, TLR2, TLR4, and NFKB1 Gene Expression in Synovial Fluid Cells of Patients with Osteoarthritis after SARS-CoV-2 Infection - Cytology and Genetics

Abstract Coronavirus disease 2019, induced by SARS-CoV-2 virus (severe acute respiratory syndrome-related coronavirus 2), has led to a huge negative impact on people’s health all around the globe, including in Ukraine. The potential effects of coronavirus infection on the course of osteoarthritis, one of the most widespread chronic degenerative joint illnesses, remains unclear. The aim of this work was to analyze the expression of COMP, TLR2, TLR4, and NFKB1 genes in synovial liquid cells as well as to establish the concentration of cytokines (IL-6, IL-8), TLR-2, and COMP in blood plasma of osteoarthritic patients that have had the SARS-CoV2 infection. The research included 75 men, aged from 45 to 55 years. The volunteers were divided into the following groups: the first group (n = 25) was conditionally healthy people, the second group (n = 25) was II–III degree knee joint osteoarthritis patients, and the third group consisted of 25 patients with II–III degree knee joint osteoarthritis after having had COVID-19. The expression levels of COMP, TLR2, TLR4, and NFKB1 genes in knee joint synovial liquid cells was measured by RT-qPCR. The concentration of IL-6, IL-8, TLR-2, and COMP was estimated with enzyme-linked immunosorbent assay. More significant decrease in the COMP gene expression in osteoarthritic patients that had COVID-19 was shown compared to the group with knee joint osteoarthritis alone on the background of more intensive COMP concentration increase in patients with osteoarthritis after SARS-CoV-2 infection. At the same time, the increase in expression levels of TLR2, TLR4, and NFKB1 was also detected as more evident in osteoarthritic patients after having COVID-19 disease if compared to the group of patients with knee joint osteoarthritis on the background of more substantial increase in IL-6, IL-8, and TLR-2 in osteoarthritic patients after having SARS-CoV-2 infection. Exacerbation of systemic inflammation due to the body’s response to viral invasion can cause such a pathological connection. The results indicate the intensification of destructive processes in the cells of the synovial fluid of patients with osteoarthritis after SARS-CoV-2 infection, which may indicate the risk of a more severe course of this disease.

PH sensitivity of cerebrospinal fluid-contacting neurons involves the modulation of phasic and tonic currents mediated by PKD2L1 channels located in the apical process.

Cerebrospinal fluid contacting neurons (CSFcNs) are GABAergic cells that surround the central canal (CC) of the spinal cord. Their soma is located sub-ependymally and they have a dendritic-like process that ends as a bulb (the so-called apical process; ApPr) inside the CC. It remains unclear how this unique anatomical organization, with the soma and the ApPr located in different extracellular environments, relates to their function as a multimodal sensor of cerebrospinal fluid (CSF) composition. One of the main physiological features of CSFcNs is a prominent spontaneous electrical activity mediated by PKD2L1 (or TRPP2) channels, a non-selective cation channel of the TRP family. PKD2L1 channels have a high single-channel conductance (around 200 pS) and can be modulated by protons and mechanical forces. In this work we investigate PKD2L1 channel sensitivity to pH and its effects on CSFcNs excitability. We demonstrate that PKD2L1 spontaneous activity generates not only phasic inward currents, but also a tonic current, both of which are modulated bidirectionally by pH with a high sensitivity around physiological values. By combining electrophysiology (direct recordings from intact and isolated ApPrs) with optical methods (laser-photolysis of protons) we further show that functional PKD2L1 channels are specifically localized in the ApPr. The spatial segregation of PKD2L1 channels, along with their biophysical properties (high single-channel conductance and pH sensitivity) and the ApPr's unique membrane properties (very high input resistance) renders CSFcN excitability exquisitely sensitive to PKD2L1 modulation. Altogether, our findings illustrate how the ApPr's properties are finely tuned to support its sensory role. ### Competing Interest Statement The authors have declared no competing interest. Agencia Nacional de Investigación e Innovación, FCE\_1\_2021\_1\_166464 Wings For Life Spinal Cord Research Foundation, WFL-UY-13/23 #290

Research Reveals How Fat Cells Can Have Fuels Of Breast Cancer Tumors Star-news.press/wp

Certain breast cancer tumors may feed on neighboring fat cells, a new study reveals. It helps uncover why being overweight is linked to higher breast cancer risk.

#MERS-related #coronavirus circulating in #pangolins exhibits strong fusogenicity in #human #cells and high sensitivity to fusion inhibitors