Synovial Fluid of Patient With Rheumatoid Arthritis Enhanced Osmotic Sensitivity Through the Cytotoxic Edema Module in Synoviocytes

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of the synovial membrane ultimately leading to permanent damage in the affected joints. For this study, synovial fluids from 16 patients diagnosed with either RA or osteoarthritis (OA) were used to examine volume regulation and cooperative water channels, both of which are involved in the cytotoxic edema identified in RA-fibroblast-like synoviocytes (FLS). The osmolarity and inflammatory cytokine interleukin (IL)-6 of synovial fluids from RA patients were mildly enhanced compared to that from OA patients. RA-FLS demonstrated the enhanced property of regulatory volume increase in response to IL-6 and synovial fluids from RA patients. Although there was no difference in the protein expression of the volume-associated protein sodium–potassium–chloride cotransporter1 (NKCC1), its activity was increased by treatment with IL-6. Membrane localization of NKCC1 was also increased by IL-6 treatment. Additionally, both the protein and membrane expressions of aquaporin-1 were increased in RA-FLS by IL-6 stimulation. The IL-6-mediated enhanced osmotic sensitivity of RA-FLS likely involves NKCC1 and aquaporin-1, which mainly constitute the volume-associated ion transporter and water channel elements. These results suggest that RA-FLS provide enhanced electrolytes and concomitant water movement through NKCC1 and aquaporin-1, thereby inducing cellular swelling ultimately resulting in cytotoxic edema. Attenuation of cytotoxic edema and verification of its related mechanism will provide novel therapeutic approaches to RA treatment within the scope of cytotoxic edema.

Osmolarity‐Induced Altered Intracellular Molecular Crowding Drives Osteoarthritis Pathology

“…a) Schematic diagram showing that the cell size can be controlled through osmolarity and the methods used to investigate the cells size. b) Literature reports on osmolarities between healthy and diseased joints (Study 1, [ 2 ] 2, [ 21 ] 3, [ 22 ] 4, [ 23 ] 5, [ 19e ] 6, [ 24 ] 7, [ 25 ] 8, [ 26 ] 9, [ 27 ] 10 [ 28 ] and 11 [ 17b ] and our [own] measurements of osmolarity of synovial fluid from OA patients); Filled squares and open circles indicate osmolarity measurements from synovial fluid and cartilage tissue, respectively. c) Fixed charge density measurements of healthy and OA cartilage tissue (Study 1, [ 19c ] 2, [ 19d ] 3, [ 19b ] 4 [ 19a ] ).…”

A Cardioplegic Solution with an Understanding of a Cardiochannelopathy

“…Furthermore, it appears that modulations of the electrolyte movements through ion channels such as SLC26A6 and its related enzyme, carbonic anhydrase, as well as through ion transporters such as NCX, NHE, and AQPs, play an important role in cardiac physiology. In our previous study in other tissues, the joint edema showed in rheumatoid arthritis (RA) patients was caused by the osmotic change of the synovium, where it was addressed that not only AQP-1 but also a combined ion transporter such as Na + -K + -2Cl − co-transporter 1 (NKCC1) and osmotic regulatory protein oxidative stress-responsive kinase 1 were involved [ 127 , 128 ]. A cytotoxic edema was induced by a pro-inflammatory cytokine such as IL-6 in RA synovial fluids from RA patients and NKCC1 was recruited to the plasma membrane of RA fibroblast-like synoviocytes and a combined volume regulation through AQP-1 was mediated [ 128 ].…”

“…In our previous study in other tissues, the joint edema showed in rheumatoid arthritis (RA) patients was caused by the osmotic change of the synovium, where it was addressed that not only AQP-1 but also a combined ion transporter such as Na + -K + -2Cl − co-transporter 1 (NKCC1) and osmotic regulatory protein oxidative stress-responsive kinase 1 were involved [ 127 , 128 ]. A cytotoxic edema was induced by a pro-inflammatory cytokine such as IL-6 in RA synovial fluids from RA patients and NKCC1 was recruited to the plasma membrane of RA fibroblast-like synoviocytes and a combined volume regulation through AQP-1 was mediated [ 128 ]. In this regard, we considered the sufficient possibility that a cardiac edema caused by an IR injury after a cardiac arrest is associated with the convergent involvement of dynamic ion transporters and AQP.…”

Validation of antioxidant, antiproliferative, and in vitro anti‐rheumatoid arthritis activities of epigallo‐catechin‐rich bioactive fraction from Camellia sinensis var. assamica , Assam variety white tea, and its comparative evaluation with green tea fraction

“…Of these, RA group includes three females and two male patients aged 50 years with disease duration of 3–4 years; while the OA group contains four females and one male patient aged 53 years with disease duration of 3–4 years. Synovial fluid was aspirated from the knee joints of all OA and RA patients included (Kay & Upchurch, 2012), fulfilling the criteria laid down by the American College of Rheumatology, 2016 (Cheng et al, 2022; Ji et al, 2021).…”

“…The study was conducted with the approval of the Institutional from the knee joints of all OA and RA patients included (Kay & Upchurch, 2012), fulfilling the criteria laid down by the American College of Rheumatology, 2016 (Cheng et al, 2022;Ji et al, 2021).…”