{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:17:10Z","timestamp":1761895030643},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,2,23]],"date-time":"2010-02-23T00:00:00Z","timestamp":1266883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p> <jats:italic>Objectives:<\/jats:italic>\u2002Bortezomib (PS\u2010341; Velcade\u2122), a proteasome inhibitor, is used as a therapeutic agent for multiple myeloma. Bortezomib has been shown to strongly induce osteoblast differentiation and elevate the levels of osteoblast\u2010related differentiation markers in the serum of patients with myeloma. Bortezomib also reportedly increases the activity of the transcription factor, Runx2. However, the mechanism of action by which bortezomib\u2010elevated Runx2 activity mediates osteoblast differentiation remains unclear. On the other hand, fibroblast growth factor 2 (FGF\u20102) is found at high levels in patients with multiple myeloma. We previously reported that FGF\u20102 reduces the levels of the transcriptional coactivator with PDZ\u2010binding motif (TAZ). We therefore investigated the effects of bortezomib on TAZ protein levels in the presence of FGF\u20102. <jats:italic>Methods:<\/jats:italic> Osteoblastic MC3T3\u2010E1 cells were treated with different concentrations of bortezomib in the presence or absence of FGF\u20102 and various biologic responses were investigated by immunoblotting, RT\u2010PCR, quantitative PCR, and alizarin red staining. <jats:italic>Results:<\/jats:italic> We found that bortezomib inhibited FGF\u20102\u2010induced reduction of TAZ levels through a pathway other than that used for proteasome inhibition, while maintaining TAZ function, which in turn, enhanced the expression of Runx2\u2010transcribed osteogenic differentiation markers. Bortezomib also suppressed the antimineralization effect of FGF\u20102. <jats:italic>Conclusions:<\/jats:italic> These findings suggest that bortezomib inhibited FGF\u20102\u2010induced reduction of TAZ and consequently stimulated osteogenic differentiation independently of proteasome inhibition. These findings may contribute to elucidate the osteolytic mechanism in multiple myeloma, and to the development of new drugs for multiple myeloma and other osteolytic diseases.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2010.01435.x","type":"journal-article","created":{"date-parts":[[2010,2,23]],"date-time":"2010-02-23T15:34:45Z","timestamp":1266939285000},"page":"68-75","source":"Crossref","is-referenced-by-count":10,"title":["The proteasome inhibitor bortezomib inhibits FGF\u20102\u2010induced reduction of TAZ levels in osteoblast\u2010like 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