RAGE, receptor for advanced glycation endoproducts (AGE), has been characterized as an activator of osteoclastgenesis. However, whether RAGE directly regulates chondrocyte proliferation and differentiation is unclear. Here, we show that RAGE has an inhibitory role in chondrocyte differentiation. RAGE expression was observed in chondrocytes from the prehypertrophic to hypertrophic regions. In cultured cells, overexpression of RAGE or dominant-negative-RAGE (DN-RAGE) demonstrated that RAGE inhibited cartilaginous matrix production, while DN-RAGE promoted production. Additionally, RAGE regulated Ihh and Col10a1 negatively but upregulated PTHrP receptor. Ihh promoter analysis and real-time PCR analysis suggested that downregulation of Cdxs was the key for RAGE-induced inhibition of chondrocyte differentiation. Overexpression of the NF-κB inhibitor I-κB-SR inhibited RAGE-induced NF-κB activation, but did not influence inhibition of cartilaginous matrix production by RAGE. The inhibitory action of RAGE was restored by the Rho family GTPases inhibitor Toxin B. Furthermore, inhibitory action on Ihh, Col10a1 and Cdxs was reproduced by constitutively active forms, L63RhoA, L61Rac, and L61Cdc42, but not by I-κB-SR. Cdx1 induced Ihh and Col10a1 expressions and directly interacted with Ihh promoter. Retinoic acid (RA) partially rescued the inhibitory action of RAGE. These data combined suggests that RAGE negatively regulates chondrocyte differentiation at the prehypertrophic stage by modulating NF-κB-independent and Rho family GTPases-dependent mechanisms.
The Industry Scale of Physical Education Classes in Elementary Schools (ISPE) was developed. Then, ISPE was used to clarify differences in Industry, which is one stage of Erickson's stages of psychosocial development, in relation to grade, gender, and flow experiences in physical education classes, as well as efforts made in other subjects. A questionnaire consisting of 43 items related to Industry was developed in a pilot study by qualitatively analyzing a unit of physical development exercise in third and fourth grades of elementary school. In the main study, elementary school students (N = 1,276, 646 boys and 630 girls) responded to this questionnaire. Exploratory and confirmatory factor analysis indicated that the ISPE consisted of four factors and 22 items: (1) Empathy for peers, (2) Discovery of challenges, (3) Initial remarks and (4) Conscientiousness.Each ISPE factor had satisfactory internal consistency, and each ISPE factor score was positively correlated with the results of fitness and physical competence tests, which confirmed its concurrent validity. Moreover, each ISPE factor score had a weak correlation with efforts made in other subjects including Japanese language and arithmetic. These results are suggestive of a common industry trait in all subjects. Moreover, a moderate ス ポ ー ツ 教 育 学 研 究 <原著論文>
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