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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Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression.

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The objective of this study was to examine the relationship between cartilage degeneration early after partial medial meniscectomy and abnormal alignment in the lower extremity. The subjects were 34 patients (37 knees) with medial meniscal tear who underwent arthroscopic partial meniscectomy. MRI was performed before and 6 months after surgery. T 2 mapping images in sagittal sections of medial femoral condyle were produced and 10 regions of interest were set at intervals of 10° in the articular cartilage in the femur. Subjects with an increase in T 2 of ≥6% at a flexion angle of 30° were assigned to the degeneration group. Patient background, hip-knee-ankle (HKA) angle, and total resection of meniscal segments were compared between this group and the other patients to identify factors involved in degeneration of articular cartilage. T 2 values 6 months after surgery in 3 ROIs at flexion angles of 30° to 50° were significantly longer than those before surgery. The preoperative HKA angle was significantly higher in the degeneration group. T 2 values in articular cartilage of the femoral condyle increased earlier after meniscectomy with abnormal alignment in the lower extremity. Meniscectomy in cases with abnormal alignment may have a risk of early onset of osteoarthritis. Level of evidence: Level IV