Brn3 transcription factors control terminal osteoclastogenesis

Ulrike Schulze-Späte, Ricardo Battaglino, Jia Fu, Anupriya Sharma, Martha Vokes, Philip Stashenko

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Osteoclastic bone resorption is a central mechanism in skeletal development, remodeling and pathology. RANKL is a mandatory factor controlling osteoclastogenesis; however, the underlying signaling pathways are only partially characterized. Using a screening array for the investigation of differential transcription factor activation, we identified activation of the Brn3 transcription factor family as a downstream event of RANKL signaling during terminal osteoclastogenesis. RANKL stimulation induces expression of Brn3a and b and maximal transcriptional activity of Brn3 family members concurrent with osteoclastic giant cell formation. Immunohistochemical analysis revealed both nuclear and cytoplasmic localization of Brn3a and b in mature osteoclasts. Functional inhibition of Brn3 transcription factors resulted in inhibition of pre-osteoclast fusion and reduction in bone resorbing activity of mature osteoclasts. Furthermore, we identified synaptotagmin-1, a regulator of membrane and vesicular fusion, as downstream target of Brn3 with a role in osteoclast function. We conclude that Brn-3 represents a novel molecular differentiation factor that controls osteoclast maturation and function, suggesting an important role in bone metabolism.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalJournal of Cellular Biochemistry
Volume102
Issue number1
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Keywords

  • Bone
  • Differentiation
  • Osteoclast
  • RANKL
  • Transcription factor

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