PTX3 Stimulates Osteoclastogenesis by Increasing Osteoblast RANKL Production. Issue 11 (November 2014)

• Record Type: Journal Article
• Authors: Lee, Eun‐Jin; Song, Da‐Hyun; Kim, Yeon‐Ju; Choi, Bongkun; Chung, Yeon‐Ho; Kim, Sang‐Min; Koh, Jung‐Min; Yoon, Seung‐Yong; Song, Youngsup; Kang, Sang‐Wook; Chang, Eun‐Ju
• Is Part Of: Journal of cellular physiology. Volume 229:Issue 11(2014:Nov.)
• Page Start: 1744
• Page End: 1752
• Publication Date: 2014-11
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24626
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jcp24626-sec-0001" sec-type="section"> <p>Pentraxin‐3 (PTX3), also known as tumor necrosis factor‐stimulated gene 14 (TSG‐14), is produced by immune and vascular cells in response to pro‐inflammatory signals and is therefore a multipotent inflammatory mediator. The present study showed that during human osteoblast (OB) differentiation, precursor OBs (pOBs), but not mature OB, highly expressed PTX3. TNFα treatment elevated the PTX3 expression of pOBs. When mice were injected with lipopolysaccharide, which induces an inflammatory osteolytic condition characterized by trabecular bone destruction and high osteoclastogenesis, their bone marrow cells expressed elevated levels of PTX3 protein. Exogenous PTX3 did not directly affect osteoclast (OC) or OB differentiation. However, when pOBs and precursor OCs were co‐cultured, exogenous PTX3 significantly increased the number of tartrate‐resistant acid phosphatase‐positive multinucleated cells (i.e., OC cells) by increasing the pOB mRNA expression and protein secretion of RANK ligand (RANKL). This was accompanied with increased Runt‐related transcription factor 2 (Runx2) expression in the pOBs. Knock‐down of endogenous PTX3 with small‐interfering RNA did not change the osteogenic potential of pOBs but suppressed their production of RANKL and reduced osteoclastogenesis. Finally, TNFα treatment of the co‐culture elevated PTX3 expression by the pOBs and increased OC formation. This effect was suppressed by PTX3 knock‐down by decreasing RANKL expression. Thus, the PTX3‐driven increase in the osteoclastogenic potential of pOBs appears to be mediated by the effect of PTX3 on pOB RANKL production. These findings suggest that PTX3 is an inflammatory mediator that contributes to the deteriorating osteolytic condition of inflamed bone. J. Cell. Physiol. 229: 1744–1752, 2014. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>