Smad1/5 and Smad4 Expression Are Important for Osteoclast Differentiation. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Tasca, Amy; Stemig, Melissa; Broege, Aaron; Huang, Brandon; Davydova, Julia; Zwijsen, An; Umans, Lieve; Jensen, Eric D.; Gopalakrishnan, Raj; Mansky, Kim C.
• Is Part Of: Journal of cellular biochemistry. Volume 116:Issue 7(2015:Jul.)
• Page Start: 1350
• Page End: 1360
• Publication Date: 2015-07
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25092
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jcb25092-sec-0001" sec-type="section"> <p>To investigate the necessity of the canonical BMP pathway during osteoclast differentiation, we created osteoclasts with a conditional gene deletion for <italic>Smad1</italic> and <italic>Smad5</italic> (SMAD1/5), or <italic>Smad4</italic> using adenovirus expressing CRE recombinase (Ad‐CRE). Reduction of either Smad4 or Smad1/5 expression resulted in fewer and smaller multinuclear cells compared to control cells. We also detected changes in osteoclast enriched genes, demonstrated by decreased <italic>Dc‐stamp</italic> and <italic>cathepsin K</italic> expression in both Smad4 and Smad1/5 Ad–CRE osteoclasts, and changes in <italic>c‐fos</italic> and <italic>Nfatc1</italic> expression in only Smad4 Ad–CRE cells. Lastly we also detected a significant decrease in resorption pits and area resorbed in both the Smad4 and Smad1/5 Ad‐CRE osteoclasts. Because we inhibited osteoclast differentiation with loss of either Smad4 or Smad1/5 expression, we assessed whether BMPs affected osteoclast activity in addition to BMP's effects on differentiation. Therefore, we treated mature osteoclasts with BMP2 or with dorsomorphin, a chemical inhibitor that selectively suppresses canonical BMP signaling. We demonstrated that BMP2 stimulated resorption in mature osteoclasts whereas treatment with dorsomorphin blocks osteoclast resorption. These results indicate that the BMP canonical signaling pathway is important for osteoclast differentiation and activity. J. Cell. Biochem. 116: 1350–1360, 2015. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>