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The bone is a metabolically active organ which undergoes repeated remodeling cycles of bone resorption and formation. In this study, we revealed a robust and extremely long-lasting circadian rhythm in ex vivo culture maintained for over six months from the femoral bone of a PERIOD2Luciferase mouse. Furthermore, we also identified robust circadian clocks in flat bones. High- or low-magnification real-time bioluminescence microscopic imaging revealed that the robust circadian rhythms emanated from the articular cartilage and the epiphyseal cartilage within the growth plate of juvenile animals. Stimulation by forskolin or dexamethasone treatment caused type 0 phase resetting, indicating canonical entraining properties of the bone clock. Together, our findings from long-term ex vivo culture revealed that “tissue-autonomous” circadian rhythm in the articular cartilage and the growth plate of femoral bone functions for several months even in an organ culture condition, and provided a useful in vitro assay system investigating the role of the biological clock in bone formation or development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In chronic lateral ankle instability (CLAI), the instability of the ankle joint results in repeated microtrauma to the articular cartilage. How the lesion condition or stage is affected by the presence of lateral instability in medial osteochondral lesions of the talus (OLT) is unclear. We aimed to examine whether CLAI is associated with the size and staging of medial OLT on radiographs, magnetic resonance (MR) images, and arthroscopy.Methods: Forty-five patients with medial OLTs in 45 ankles were reviewed. Radiographs were assessed for damage and lesion classification. The tibio-talar tilting angle (TTA) was measured. The patients were divided into two groups: the CLAI group and the stable group. The lesion classification on radiographs, MR images, and arthroscopy, and size on MR images were statistically compared.Results: The CLAI group had a mean TTA of 8.15 ± 3.41°, whereas the stable group had a mean TTA of 2.24 ± 1.64°. The CLAI group had a lower clinical score than the stable group at the initial visit to our clinic. The CLAI group presented with lesions of significantly shorter longitudinal and transverse diameters. Stages of medial OLT on radiographs, MR images, and arthroscopic evaluation were earlier in the CLAI group than those in the stable group.Conclusions: Patients with CLAI presented in the early stages of OLT and had significantly smaller lesions than those without CLAI. The patients without CLAI may be selected for surgery at an early phase. [ABSTRACT FROM AUTHOR]