Expression of Connexin 43 in Synovial Tissue of Patients With Rheumatoid Arthritis

Matsuki, Tomohiro; Tsuchida, Shinji; Terauchi, Ryu; Oda, Ryo; Fujiwara, Hiroyoshi; Mazda, Osam; Kubo, Toshikazu

doi:10.5606/archrheumatol.2016.5597

Cited by 9 publications

(8 citation statements)

References 26 publications

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“…We also analyzed the role of Cx43 as a key gene in synovial membrane inflammation in RA. Studies have shown that, in collagen-induced arthritis (CIA) rats, Cx43 induces joint destruction through pro-inflammatory cytokines such as TNF-α and IL-6, and that joint destruction is suppressed not only if Cx43 expression is suppressed in small interfering ribonucleic acid, but also by suppressing Cx43 expression through treadmill running as well [17,23,24]. Cx43 expression changes with mechanical stress such as stretching stimuli and shearing forces in cardiomyocytes and osteocytes [25,26]; therefore, it may also change due to the addition of mechanical stress to the synovial membranes by treadmill running.…”

Section: Discussionmentioning

confidence: 99%

Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models

Fujii

Inoue

Shimomura

et al. 2019

IJMS

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Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.

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Section: Discussionmentioning

confidence: 99%

Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models

Fujii

Inoue

Shimomura

et al. 2019

IJMS

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“…We previously reported that Cx43 in the CIA rat synovial membrane induced joint destruction via pro-inflammatory cytokines such as TNF-α and IL-6 and joint destruction was suppressed by downregulating Cx43 [ 17 ]. We also reported the cross-talk between Cx43 and TNF-α in human synovial fibroblasts [ 20 ]. In the present study, Cx43 in the CIA group was produced in the synovial membrane at the same level as TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model

Shimomura

Inoue

Nakagawa

et al. 2018

IJMS

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We analyzed the influence of treadmill running on rheumatoid arthritis (RA) joints using a collagen-induced arthritis (CIA) rat model. Eight-week-old male Dark Agouti rats were randomly divided into four groups: The control group, treadmill group (30 min/day for 4 weeks from 10-weeks-old), CIA group (induced CIA at 8-weeks-old), and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by μ-CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of tumor necrosis factor-α and Connexin 43; production was significantly suppressed by treadmill running. On μ-CT of the talus, bone volume fraction (BV/TV) was significantly decreased in the CIA group. Marrow star volume (MSV), an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. Bone destruction in the talus was significantly increased with CIA and was suppressed by treadmill running. On tartrate-resistant acid phosphate and alkaline phosphatase (TRAP/ALP) staining, the number of osteoclasts around the pannus was decreased by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction.

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“…In their study, Schierbeck et al reported that the TNF-α secretion induced in monocytes stimulated by LPS (lipopolysaccharide) + IFN-γ (interferon-γ) was significantly decreased when the cells were pretreated for one hour with the anti-TNF-α etanercept at either 2 or 8 µg/mL, whereas the anti-IL-1β anakinra (from 2.5 to 20 µg/mL) didn't show any effect on the TNF-α secretion [34]. Furthermore, the gap junction mediator connexin-43 (Cx43) was shown to be involved in both gene expression and secretion of the TNF-α and IL-6 cytokines in a human RA synovial fibroblast model [35]. Matsuki et al indeed showed that the siRNA-mediated Cx43 inhibition impaired the expression of these cytokines.…”

Section: Ra and Cytokines: A Tnf-α And Il-1β Crosstalk Modeled Both In Vitro And In Vivomentioning

confidence: 99%

Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Rationale of the 2LARTH® Micro-Immunotherapy Treatment

Jacques¹,

Floris²,

Lejeune³

2021

IJMS

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Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are two cytokines involved in the perpetuation of the chronic inflammation state characterizing rheumatoid arthritis (RA). Significant advances in the treatment of this pathology have been made over the past ten years, partially through the development of anti-TNF and anti-IL-1 therapies. However, major side effects still persist and new alternative therapies should be considered. The formulation of the micro-immunotherapy medicine (MIM) 2LARTH® uses ultra-low doses (ULD) of TNF-α, IL-1β, and IL-2, in association with other immune factors, to gently restore the body’s homeostasis. The first part of this review aims at delineating the pivotal roles played by IL-1β and TNF-α in RA physiopathology, leading to the development of anti-TNF and anti-IL-1 therapeutic agents. In a second part, an emphasis will be made on explaining the rationale of using multiple therapeutic targets, including both IL-1β and TNF-α in 2LARTH® medicine. Particular attention will be paid to the ULD of those two main pro-inflammatory factors in order to counteract their overexpression through the lens of their molecular implication in RA pathogenesis.

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Expression of Connexin 43 in Synovial Tissue of Patients With Rheumatoid Arthritis

Cited by 9 publications

References 26 publications

Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models

Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models

Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model

Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as the Rationale of the 2LARTH® Micro-Immunotherapy Treatment

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