著者

Yoshinao HOSAKA Sachiko OZOE Rikio KIRISAWA Hiromi UEDA Kazushige TAKEHANA Mamoru YAMAGUCHI

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.27, no.5, pp.233-241, 2006 (Released:2006-11-13)

参考文献数

46

被引用文献数

11 20

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The aim of this study was to clarify whether matrix metalloproteinases (MMP-2 and -9: gelatinases) and pro-inflammatory cytokines [tumor necrosis factor (TNF) α and interleukin (IL)-1β] are induced by heat in tendon tissue in vitro and to test the hypothesis that heat exposure causes tendinocytes to synthesize pro-inflammatory cytokines and that synthesis of these cytokines, in turn, leads to up-regulation of synthesis of gelatinases. Isolated tendinocytes from equine superficial digital flexor tendons were cultured and all experiments were performed on cells passaged 3 or 4 times. In the cells exposed to heat (37 to 45°C, 0 to 60 min), the survival rate decreased sharply in a temperature- and time-dependent manner, especially at 42 and 45°C. Cells exposed at 40°C, however, showed little change in survival rate and morphology. Gelatin zymograms revealed that proMMP-2 and -9 were the only two MMPs remaining in the supernatant of the cultured tendinocytes, including that of untreated cells. Addition of TNFα and IL-1β to the culture medium of tendinocytes accelerated proMMP-9 synthesis considerably. Heating the tendinocytes (40°C) led to a three-fold increase in proMMP-9 synthesis in a short time. Only TNFα was detected in tendinocytes after heat exposure for 30 and 60 min. In contrast, IL-1β was under the detectable level in ELISA. Cooling of heat-exposed cells from 40°C to 37°C considerably down-regulated cellular proMMP-9 synthesis. Furthermore, proMMP-9 level was greatly reduced in cells treated at lower temperatures, 20°C and 5°C. These findings support our hypothesis that hyperthermia in the horse tendon induces tendinocytes to synthesize pro-inflammatory cytokines and that the synthesis of these cytokines results in the up-regulation of gelatinases.

著者

Takeshi YAMAUCHI Takuya HIROSE Kaho SATO Kenji IWAI Naoki TAKAHASHI Jun MINAGUCHI Takeshi UENO Prasarn TANGKAWATTANA Kazushige TAKEHANA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0206, (Released:2017-08-04)

被引用文献数

3

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Ehlers-Danlos syndrome (EDS) is a group of disorders caused by abnormalities in the extracellular matrix (ECM). Transforming growth factor-β (TGF-β) plays a crucial role in formation of the ECM by the SMAD (Sma-and Mad-related protein, mothers against decapentaplegic homolog) pathway. It has been reported that loss of function of zinc transporter ZRT/IRT-like protein 13 (ZIP13) is the cause of the spondylocheiro dysplastic form of EDS (SCD-EDS: OMIM 612350). Our previous study suggested that TGF-β1 has a relationship with the skin pathological condition in the Zip13-Knockout (KO) mouse, which is a model of SCD-EDS. Thus far, effective treatment based on modern medicine for this syndrome has not yet been established. According to an approach of traditional Chinese medicine, the present study investigates the medicinal effects of Makomo (Zizania latifolia) on certain aspects of SCD-EDS, such as skin morphology and plasma TGF-β1, in Zip13-KO mice. Increases in densities of collagen fibers and fibrils without a significant change in thickness of the dermal layer were observed in the group of mice fed a Makomo-containing diet. No change in the amount of collagen suggests that Makomo feed does not elevate collagen synthesis, but changes the length of glycosaminoglycan chains and decreases the distance between collagen fibrils. In conclusion, the changes of the skin structure suggest that Makomo can increase the mechanical strength of skin.