Objective
This study tested the effects of bisphosphonates (BPs) on the suppressor of cytokine
signaling 3 (SOCS3) protein in macrophages. SOCS3 has been shown to regulate cell
differentiation and survival; however, its potential role in mediating the effects
of BPs has not been explored.
Study design
The cell viability of murine RAW 267.4 macrophages was assessed after culturing with
control medium or media containing increasing concentrations of 2 BPs (ibandronate
or clodronate) for 24, 48, and 72 hours. The phosphorylation status of signal transducer
and activator of transcription 3 (STAT3) and the expression of SOCS3 protein levels
were determined by Western blot analysis.
Results
In control cultures, STAT3 phosphorylation and STAT3 and SOCS3 protein levels increased
within 5 minutes after the addition of fresh medium. This increase was inhibited in
cultures treated with both BPs. Macrophage cell viability also decreased after BP
treatment.
Conclusions
These data demonstrate that, in addition to their effects on macrophage viability,
BPs can decrease STAT3 and SOCS3 expression, which are important modulators of immune
responses and bone homeostasis.
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Article info
Publication history
Accepted:
September 19,
2010
Received in revised form:
September 15,
2010
Received:
July 29,
2010
Footnotes
Supported by the Baylor Oral Health Foundation and the Texas A&M Health Science Center.
Identification
Copyright
© 2011 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Bisphosphonates that lack a nitrogen-containing side chain do not cause osteonecrosis of the jaws, regardless of their effect on STAT3 phosphorylation and SOCS3 expressionOral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and EndodonticsVol. 112Issue 6
- PreviewThe article by Jayne S. Reuben et al.1 hails a discovery of immunologic and pharmacologic significance that is largely irrelevant to the understanding of bisphosphonate-related osteonecrosis of the jaws. These nondentist researchers have made a very significant and novel discovery that bisphosphonates, with and without a nitrogenous side chain, are inflammatory cytokine modulators vis-à-vis the downregulation of macrophage suppressor of cytokine signaling 3 (SOCS3). They successfully induced this effect in vitro with macrophages exposed to clodronate and ibandronate.
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