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Time and dose dependent of IS on osteoclastogenesis. Short-term exposure in a low IS dose and ARNT are available, and AhR works as a ligand-activated transcription factor, increasing NFATc1 expression, and thus increasing osteoclastogenesis. On the contrary, long-term exposure in high doses of IS and ARNT are inaccessible, and AhR functions as an E3 ubiquitin ligase, leading to the proteasomic degradation of NFATc1 and thereby inhibiting osteoclastogenesis.
