Genetic deficiency of nuclear factor of activated T cells 5 attenuates the development of osteoarthritis in mice

Lee, Jin‐Hee; Lee, Jongmin; Lee, Saseong; Yoo, Sehoon; Kim, Ki-Myo; Kim, Wan‐Uk; Cho, Chul-Soo; Yoon, Chong‐Hyeon

doi:10.1016/j.jbspin.2021.105273

Cited by 3 publications

(3 citation statements)

References 33 publications

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“…The interdependence of NFAT5 and inflammation is also important. In line with this notion, NFAT5 can be upregulated not only by osmotic stress but also by inflammatory cytokines [ 66 ]. Although both mechanical loading protocols increase intracellular Na + concentrations and NFAT5 expression, the effects on inflammatory and bone remodeling genes are not uniform.…”

Section: Discussionmentioning

confidence: 88%

Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts

Proff,

Nazet,

Schröder

et al. 2024

Cells

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Osteoarthritis (OA) is a multifactorial disease depending on molecular, genetic, and environmental factors like mechanical strain. Next to the cartilage and the subchondral bone, OA also affects the synovium, which is critically involved in the maintenance of joint homeostasis. As there is a correlation between the extracellular sodium content in the knee joint and OA, this study investigates the impact of sodium on OA-associated processes like inflammation and bone remodeling without and with mechanical loading in synovial fibroblasts. For that purpose, murine synovial fibroblasts from the knee joint were exposed to three different extracellular sodium chloride concentrations (−20 mM, ±0 mM and +50 mM NaCl) in the absence or presence of compressive or intermittent tensile strain. In addition to the intracellular Na+ content and gene expression of the osmoprotective transcription factor nuclear factor of activated T cells 5 (Nfat5), the gene and protein expression of inflammatory mediators (interleukin-6 (IL6), prostaglandin endoperoxide synthase-2 (Ptgs2)/prostaglandin E2 (PGE2)), and factors involved in bone metabolism (receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG)) were analyzed by qPCR and ELISA. Mechanical strain already increased intracellular Na+ and Nfat5 gene expression at standard salt conditions to levels obtained by exposure to increased extracellular Na+ content. Both high salt and compressive strain resulted in elevated IL6 and PGE2 release. Intermittent tensile strain did not increase Il6 mRNA expression or IL6 protein secretion but triggered Ptgs2 expression and PGE2 production. Increased extracellular Na+ levels and compressive strain increased RANKL expression. In contrast, intermittent tension suppressed RANKL expression without this response being subject to modification by extracellular sodium availability. OPG expression was only induced by compressive strain. Changes in extracellular Na+ levels modified the inflammatory response and altered the expression of mediators involved in bone metabolism in cells exposed to mechanical strain. These findings indicate that Na+ balance and Nfat5 are important players in synovial fibroblast responses to mechanical stress. The integration of Na+ and Na+-dependent signaling will help to improve the understanding of the pathogenesis of osteoarthritis and could lead to the establishment of new therapeutic targets.

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Section: Discussionmentioning

confidence: 88%

Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts

Proff,

Nazet,

Schröder

et al. 2024

Cells

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“…This inducible costimulatory ligand participates in T‐cell induction, signifying that such aggregates are zones of antigen detection and T‐cell activation (Keller et al, 2022). Studies have evidenced the critical role of Th1, Th9, and Th17 in OA pathogenesis (Lee et al, 2022). Eventually, recent findings support a relation between intra‐articular concentrations of several adipokines and OA severity (Bas et al, 2014).…”

Section: The Pathophysiology Of Oamentioning

confidence: 99%

“…This inducible costimulatory ligand participates in T-cell induction, signifying that such aggregates are zones of antigen detection and Tcell activation (Keller et al, 2022). Studies have evidenced the critical role of Th1, Th9, and Th17 in OA pathogenesis (Lee et al, 2022).…”

Section: The Pathophysiology Of Oamentioning

confidence: 99%

Recent advances in mesenchymal stem/stromal cells (MSCs)‐based approaches for osteoarthritis (OA) therapy

Hassanzadeh

Vousooghi

Rahimnia

et al. 2023

Cell Biology International

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Immunoregulation of synovial macrophages for the treatment of osteoarthritis

2023

Open Life Sciences

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Osteoarthritis (OA) is the most common joint disease affecting approximately 10% of men and 18% of women older than 60. Its pathogenesis is still not fully understood; however, emerging evidence has suggested that chronic low-grade inflammation is associated with OA progression. The pathological features of OA are articular cartilage degeneration in the focal area, including new bone formation at the edge of the joint, subchondral bone changes, and synovitis. Conventional drug therapy aims to prevent further cartilage loss and joint dysfunction. However, the ideal treatment for the pathogenesis of OA remains to be defined. Macrophages are the most common immune cells in inflamed synovial tissues. In OA, synovial macrophages undergo proliferation and activation, thereby releasing pro-inflammatory cytokines, including interleukin-1 and tumor necrosis factor-α, among others. The review article discusses (1) the role of synovial macrophages in the pathogenesis of OA; (2) the progress of immunoregulation of synovial macrophages in the treatment of OA; (3) novel therapeutic targets for preventing the progress of OA or promoting cartilage repair and regeneration.

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Genetic deficiency of nuclear factor of activated T cells 5 attenuates the development of osteoarthritis in mice

Cited by 3 publications

References 33 publications

Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts

Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts

Recent advances in mesenchymal stem/stromal cells (MSCs)‐based approaches for osteoarthritis (OA) therapy

Immunoregulation of synovial macrophages for the treatment of osteoarthritis

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