QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online September 19, 2007
doi: 10.1242/10.1242/jcs.008300

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yang, S. Articles by Li, Y.-P. Search for Related Content PubMed PubMed Citation Articles by Yang, S. Articles by Li, Y.-P. Social Bookmarking                         What's this?

Specificity of RGS10A as a key component in the RANKL signaling mechanism for osteoclast differentiation

Department of Cytokine Biology, The Forsyth Institute, Boston, MA 02115, USA Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA

^* Author for correspondence (e-mail: ypli{at}forsyth.org)

Accepted 18 July 2007

Significant progress has been made in studies of the mechanisms by which RANKL induces terminal osteoclast differentiation. However, many crucial details in the RANKL-evoked signaling pathway for osteoclast differentiation remain to be defined. We characterized genes specifically expressed in osteoclasts by differential screening of a human osteoclastoma cDNA library, and found that the regulator of G-protein signaling 10A (RGS10A), but not the RGS10B isoform, was specifically expressed in human osteoclasts. The expression of RGS10A is also induced by RANKL in osteoclast precursors and is prominently expressed in mouse osteoclast-like cells. RGS10A silencing by RNA interference blocked intracellular [Ca²⁺]i oscillations, the expression of NFAT2, and osteoclast terminal differentiation in both bone marrow cells and osteoclast precursor cell lines. Reintroduction of RGS10A rescued the impaired osteoclast differentiation. RGS10A silencing also resulted in premature osteoclast apoptosis. RGS10A silencing affected the RANKL-[Ca²⁺]i oscillation-NFAT2 signaling pathway but not other RANKL-induced responses. Our data demonstrate that target components of RGS10A are distinct from those of RGS12 in the RANKL signaling mechanism. Our results thus show the specificity of RGS10A as a key component in the RANKL-evoked signaling pathway for osteoclast differentiation, which may present a promising target for therapeutic intervention.

Key words: Differential screening, RGS10 RNA interference, [Ca²⁺]i oscillations, Osteoclast differentiation, RANKL signaling pathway

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?