Enhancing Cartilage Metabolism in Rats through a Novel Thermal Stimulation Technique with Photosensitizers.

Although the moderate thermal stimulation of articular cartilage exerts chondroprotective effects, it is difficult to effectively heat deep articular cartilage with conventional methods. Photosensitizers increase the ambient temperature using near-infrared (NIR) radiation, which has high tissue permeability. We hypothesized that the intra-articular administration of photosensitizers and NIR irradiation would exert a greater heating effect on articular cartilage. We aimed to evaluate the heating effect of this method on cultured chondrocytes and rat knee cartilage. In vitro, we irradiated a photosensitizer-containing medium with NIR and measured changes in the medium temperature, cytotoxicity, and gene expression of heat shock protein (HSP) 70 and aggrecan (ACAN). In vivo, the knee joints of rats treated with photosensitizers were irradiated with NIR, and changes in intra-articular temperature and gene expression were measured, alongside histological analysis. The results showed that the medium and intra-articular temperature were raised to approximately 40 °C with no apparent disruption to articular cartilage or the immunohistochemically enhanced staining of HSP70 in chondrocytes. The gene expression of HSP70 and ACAN was increased in both cultured and articular cartilage. In summary, this method can safely heat joints and enhance cartilage metabolism by inducing HSP70 expression in articular cartilage. It presents a new hyperthermia therapy with effective cartilage protection.

Hypoxia with or without Treadmill Exercises Affects Slow-Twitch Muscle Atrophy and Joint Destruction in a Rat Model of Rheumatoid Arthritis.

The effects of treadmill running under hypoxic conditions on joints and muscles of collagen-induced arthritis (CIA) rats were investigated. CIA rats were divided into normoxia no-exercise, hypoxia no-exercise (Hypo-no), and hypoxia exercise (Hypo-ex) groups. Changes were examined on days 2 and 44 of hypoxia with or without treadmill exercises. In the early stage of hypoxia, the expression of hypoxia-inducible factor (HIF)-1α increased in the Hypo-no and Hypo-ex groups. The expression of the egl-9 family hypoxia-inducible factor 1 (EGLN1) and vascular endothelial growth factor (VEGF) in the Hypo-ex group also increased. Under sustained hypoxia, the Hypo-no and Hypo-ex groups did not show increased expression of HIF-1α or VEGF, but p70S6K levels were elevated. Histologically, joint destruction was alleviated in the Hypo-no group, the loss of muscle weight in slow-twitch muscles was prevented, and muscle fibrosis was suppressed. In the Hypo-ex group, the preventive effect of a reduction in the slow-twitch muscle cross-sectional area was enhanced. Thus, chronic hypoxia in an animal model of rheumatoid arthritis controlled arthritis and joint destruction and prevented slow-twitch muscle atrophy and fibrosis. The combination of hypoxia with treadmill running further enhanced the preventive effects on slow-twitch muscle atrophy.