Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin b expression by rat normal chondrocytes

Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1beta expression was also signifi cantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1beta. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1beta expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes.</p

情報技術を用いた浮世絵師写楽の役者絵の目に関する研究

東洲斎写楽の現存する浮世絵版画141点のうち、第一期作28点は写楽の作品で最も人気があり、それらすべてが役者絵である。役者絵なので女性の絵もすべて男性が演じているものである。写楽は女性の絵画を1点も残していないとされている。しかしその女性絵画は男性が演じているにもかかわらず女性の特徴を持つ。そこで写楽の浮世絵版画の第一期作の役者絵を男女に分けて目に焦点を当てて分析をおこなった。ある男役の順に男女12種類の目を当てはめたものを作り、被験者10人に対して男性の目か女性の目かという判断を行った。その際、女性の目を男性の顔に当てはめても明らかに違和感があるものはなかったが、女性の目を男性の目と区別できる人が多かった。そこで判別分析を用いて目の形状から男女の目の判別を行った。その結果、F_x=4.713Z_1-2.804Z_2+2.274Z_3-2.788という線形判別関数で男女の目を判別することができた。そして男女の目の判別において目の交差角が最も影響を与えることがわかった。次に上で求めた線形判別関数に実際の数値を代入し結果を求めた。その結果、男性の目でありながら女性の目であると判別されたものは1点だけであった。この目は女性の目であると判断されることが多かった目であった。すなわち、すべて男性でありながら男役と女役ではそれぞれの目を用いて男女の区別を行い、役者の特徴を出していることがわかった。目の交差角の分布をもとに6グループに分類し各グループから1つずつ目を選び男女の順に当てはめたものを作った。それらを画面に一度に表示し、30ペア60種類の感情表現を表示し最も当てはまると思われる絵画を被験者に選んでもらうことから男女の目をいろいろと変えることによって、目だけを変えた役者からどのようなイメージをうけるかという実験結果を得た。その結果、男女どちらの場合であっても男役の目を当てはめたほうが多くのプラスイメージの感情表現を得ることができ、女役の目を当てはめたときにはマイナスイメージの感情表現を得た。また、ディスプレイ上に絵画を一枚ずつ表示し対になる感情表現を与えSD (Semantic Differential)法を用いて分析を行っても、女性の目を当てはめたときのほうがマイナスイメージを与えるということがわかった。In the 141 Sharaku Ukiyo-E prints in existence, the first 28 works are the most popular in the world. These prints are all depictions of Kabuki actors. In Kabuki, a man plays every performer including those of the women. As a result, there are no Sharaku prints of actual women. However , Sharaka represents both the male and female characters in his prints. This thesis is the study on the male and female eyes of the Kabuki actors. A structure was applied to 12 kinds of men and women\u27s eyes on the face of a male role. Ten subjects had to judge whether female or male eyes are depicted. The result was that the female eye was more easily distinguished from the pictures. Therefore, it was analyzed by discriminate analysis the angle of the eyes from the analysis. In this analysis, F_x=4.713Z_1-2.804Z_2+2.274Z_3-2.788 was shown as a linear discriminate function. It was shown that the crossed axes angle of an eye had the greatest affect. Next, the discrimination point was evaluated from linear discriminate function. The eye of a certain male in one of the picture was distinguished to be that of a woman. In this analysis, although a man plays both male and female role, it turned out that men and women were distinguished in their eyes, and a feature of Kabuki actors is expressed. A model of six pictures of a male role and a female role was built based on the crossed axes angle of an eye. They were all displayed on a flat display at the same time. A subject had to select a picture that was the most proper to the certain feeling expression. The experiment using the semantic differential method showed what image the subject received from the pictures where only the eyes had changed. As a result, the eye of a male role that was applied gave subjects some positive feeling expressions, and the eye of a female role gave a negative feeling expressions. The pictures of six female roles were ordered to expression of "feminine" using a paired comparison method. As a result, the most feminine and the least feminine eyes were found, and it turned out that the others were organized by preference of the subject. In conclusion, when Sharaku drew a Kabuki actor, he distinguished their roles as a male and female by their eyes. The eye of a male role expressed positive feelings to the subjects and the eye of a female role expressed negative feelings. It showed that the eye that gave the subjects the most famine image was that of an eye that was used in a male role

Activation of AMPA Receptors in the Suprachiasmatic Nucleus Phase-Shifts the Mouse Circadian Clock In Vivo and In Vitro

The glutamatergic neurotransmission in the suprachiasmatic nucleus (SCN) plays a central role in the entrainment of the circadian rhythms to environmental light-dark cycles. Although the glutamatergic effect operating via NMDAR (N-methyl D-aspartate receptor) is well elucidated, much less is known about a role of AMPAR (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor) in circadian entrainment. Here we show that, in the mouse SCN, GluR2 and GluR4 AMPAR subtypes are abundantly expressed in the retinorecipient area. In vivo microinjection of AMPA in the SCN during the early subjective night phase-delays the behavioral rhythm. In the organotypic SCN slice culture, AMPA application induces phase-dependent phase-shifts of core-clock gene transcription rhythms. These data demonstrate that activation of AMPAR is capable of phase-shifting the circadian clock both in vivo and in vitro, and are consistent with the hypothesis that activation of AMPA receptors is a critical step in the transmission of photic information to the SCN

A light-induced small G-protein gem limits the circadian clock phase-shift magnitude by inhibiting voltage-dependent calcium channels

光誘導物質による新しい体内時計の同調制御機構 --光により誘導される神経細胞の活動抑制物質の発見--. 京都大学プレスリリース. 2022-05-26.Calcium signaling is pivotal to the circadian clockwork in the suprachiasmatic nucleus (SCN), particularly in rhythm entrainment to environmental light-dark cycles. Here, we show that a small G-protein Gem, an endogenous inhibitor of high-voltage-activated voltage-dependent calcium channels (VDCCs), is rapidly induced by light in SCN neurons via the calcium (Ca²⁺)-mediated CREB/CRE transcriptional pathway. Gem attenuates light-induced calcium signaling through its interaction with VDCCs. The phase-shift magnitude of locomotor activity rhythms by light, at night, increases in Gem-deficient (Gem⁻/⁻) mice. Similarly, in SCN slices from Gem⁻/⁻ mice, depolarizing stimuli induce larger phase shifts of clock gene transcription rhythms that are normalized by the application of an L-type VDCC blocker, nifedipine. Voltage-clamp recordings from SCN neurons reveal that Ca²⁺ currents through L-type channels increase in Gem⁻/⁻ mice. Our findings suggest that transcriptionally activated Gem feeds back to suppress excessive light-evoked L-type VDCC activation, adjusting the light-induced phase-shift magnitude to an appropriate level in mammals