Notch Signaling Promotes Osteoclast Maturation and Resorptive Activity. Issue 11 (9th September 2015)

• Record Type: Journal Article
• Authors: Ashley, Jason W.; Ahn, Jaimo; Hankenson, Kurt D.
• Is Part Of: Journal of cellular biochemistry. Volume 116:Issue 11(2015:Nov.)
• Page Start: 2598
• Page End: 2609
• Publication Date: 2015-09-09
• Subjects: Osteoclasts -- Notch signaling -- Bone resorption -- Osteoclast fusion -- Osteoclast commitment; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25205
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: The role of Notch signaling in osteoclast differentiation is controversial with conflicting experimental evidence indicating both stimulatory and inhibitory roles. Differences in experimental protocols and in vivo versus in vitro models may explain the discrepancies between studies. In this study, we investigated cell autonomous roles of Notch signaling in osteoclast differentiation and function by altering Notch signaling during osteoclast differentiation using stimulation with immobilized ligands Jagged1 or Delta‐like1 or by suppression with γ‐secretase inhibitor DAPT or transcriptional inhibitor SAHM1. Stimulation of Notch signaling in committed osteoclast precursors resulted in larger osteoclasts with a greater number of nuclei and resorptive activity whereas suppression resulted in smaller osteoclasts with fewer nuclei and suppressed resorptive activity. Conversely, stimulation of Notch signaling in osteoclast precursors prior to induction of osteoclastogenesis resulted in fewer osteoclasts. Our data support a mechanism of context‐specific Notch signaling effects wherein Notch stimulation inhibits commitment to osteoclast differentiation, but enhances the maturation and function of committed precursors. J. Cell. Biochem. 116: 2598–2609, 2015. © 2015 Wiley Periodicals, Inc.