Estrogen Decreases Osteoclast Formation by Down-regulating Receptor Activator of NF-κB Ligand (RANKL)-induced JNK Activation

Sunil Srivastava, Gianluca Toraldo, M. Neale Weitzmann, Simone Cenci, F. Patrick Ross, Roberto Pacifici

Research output: Contribution to journalArticlepeer-review

Abstract

The differentiation of cells of the monocytic lineage into mature osteoclasts (OC) is specifically induced by the tumor necrosis factor-related factor, RANKL (receptor activator of NF-κB ligand; also known as OPGL, ODF, or TRANCE). Because inhibition of osteoclastogenesis is one of the main mechanisms by which estrogen (E2) prevents bone loss, it is likely that E2 may regulate either the production of, or the target cell responsiveness to RANKL. We found that E2 decreases the differentiation into OC of both murine bone marrow monocytes and RAW 264.7 cells, a monocytic line, by down-regulating the activation of Jun N-terminal kinase 1 (JNK1). Diminished JNK1 activity results in decreased nuclear levels of the key osteoclastogenic transcription factors, c-Fos and c-Jun, and lower binding of these transcriptional inducers to DNA. Thus, one novel mechanism by which E2 down-regulates osteoclastogenesis is by decreasing the responsiveness of OC precursors to RANKL.

Original languageEnglish
Pages (from-to)8836-8840
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number12
DOIs
Publication statusPublished - Mar 23 2001

ASJC Scopus subject areas

  • Biochemistry

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