RESUMEN
Estrogen plays an important role in osteoporosis prevention. We herein report the possible novel signaling pathway of 17ß-estradiol (E2) in the matrix mineralization of MC3T3-E1, an osteoblast-like cell line. In the culture media-containing stripped serum, in which small lipophilic molecules such as steroid hormones including E2 were depleted, matrix mineralization was significantly reduced. However, the E2 treatment induced this. The E2 effects were suppressed by ICI182,780, the estrogen receptor (ER)α, and the ERß antagonist, as well as their mRNA knockdown, whereas Raloxifene, an inhibitor of estrogen-induced transcription, and G15, a G-protein-coupled estrogen receptor (GPER) 1 inhibitor, had little or no effect. Furthermore, the E2-activated matrix mineralization was disrupted by PMA, a PKC activator, and SB202190, a p38 MAPK inhibitor, but not by wortmannin, a PI3K inhibitor. Matrix mineralization was also induced by the culture media from the E2-stimulated cell culture. This effect was hindered by PMA or heat treatment, but not by SB202190. These results indicate that E2 activates the p38 MAPK pathway via ERs independently from actions in the nucleus. Such activation may cause the secretion of certain signaling molecule(s), which inhibit the PKC pathway. Our study provides a novel pathway of E2 action that could be a therapeutic target to activate matrix mineralization under various diseases, including osteoporosis.
Asunto(s)
Estradiol , Osteoblastos , Transducción de Señal , Animales , Ratones , Estradiol/farmacología , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Calcificación Fisiológica/efectos de los fármacos , Línea Celular , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Estrógenos/farmacología , Estrógenos/metabolismo , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/genéticaRESUMEN
Background: The spread of the coronavirus disease (COVID-19) has significantly affected medical education. In particular, conducting practical training in a face-to-face format has become difficult. Purpose: To address this problem, online physiology practice combined with team-based learning (TBL) for deep learning of renal physiology was conducted among second-year medical students. Participants and Methods: The experiment was performed by a group of students, while other students watched online. After the experiment, all students were grouped using breakout rooms. Following a discussion of the data, a clinical case study related to the experiment was conducted using TBL. To examine the effect of online practice in a case study under TBL, the participants completed an anonymous, open-ended, web-based questionnaire after the program, enabling us to compare their expectations and satisfaction. The questionnaire consisted of questions examining students' opinions on the appropriateness of online practice, degree of understanding, ease of asking questions, time efficiency, and the usefulness of case studies using TBL. Results: There was no change in the number of students who participated in the online practice before and after class. After class, more students considered the level of understanding easier and displayed better on-time efficiency than with regular face-to-face training. However, these questions are difficult to answer. Conclusion: Online-based physiology practice combined with clinical case studies under TBL helped maintain students' expectations and satisfaction with the training.