Role of direct estrogen receptor signaling in wear particle-induced osteolysis

Christophe Nich, Allison J. Rao, Roberto D. Valladares, Chenguang Li, Jane E. Christman, Joseph K. Antonios, Zhenyu Yao, Stefan Zwingenberger, Hervé Petite, Moussa Hamadouche, Stuart B. Goodman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Estrogen withdrawal following surgical ovariectomy was recently shown to mitigate particle-induced osteolysis in the murine calvarial model. Currently, we hypothesize that estrogen receptors (ERs) were involved in this paradoxical phenomenon. To test this hypothesis, we first evaluated polyethylene (PE) particle-induced osteolysis in the murine calvarial model, using wild type (WT) C57BL6J female mice, ERα deficient (ERαKO) mice, and WT mice either treated with 17. β-estradiol (E2) or with the ER pan-antagonist ICI 182,780. According to micro-CT and histomorphometry, we showed that bone resorption was consistently altered in both ERαKO and ICI 182,780 treated mice as compared to WT and E2 groups. Then, we demonstrated that ER disruption consistently decreased both PE and polymethylmethacrylate (PMMA) particle-induced production of TNF-α by murine macrophages in vitro. Similar results were obtained following ER blockade using ICI 182,780 in RAW 264.7 and WT macrophages. ER disruption and pre treatment with ICI 182,780 resulted in a consistent down-regulation of particle-induced TNF-α mRNA expression relative to WT macrophages or untreated RAW cells. These results indicate that the response to wear particles involves estrogen receptors in female mice, as part of macrophage activation. Estrogen receptors may be considered as a future therapeutic target for particle-induced osteolysis.

Original languageEnglish (US)
Pages (from-to)641-650
Number of pages10
Issue number3
StatePublished - Jan 2013
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank Dr. Timothy Wright (Hospital for Special Surgery, New York, NY) for the generous gift of UHMWPE particles. This work was supported by the Robert L. and Mary Ellenburg Chair in Surgery, Stanford University, L'Assistance Publique – Hôpitaux de Paris (AP-HP) , La Société Française de Chirurgie Orthopédique (SOFCOT) , and Le Centre National de la Recherche Scientifique (CNRS UMR 7052) , Paris, France.


  • Estrogen receptor
  • Macrophages
  • Osteolysis
  • Polyethylene
  • Wear debris


Dive into the research topics of 'Role of direct estrogen receptor signaling in wear particle-induced osteolysis'. Together they form a unique fingerprint.

Cite this