title: PTX3 stimulates osteoclastogenesis by increasing osteoblast RANKL production.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Da-Hyun
authors.initials: DH
authors.lastname: Song
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Bongkun
authors.initials: B
authors.lastname: Choi
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Chung
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Koh
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
authors.forename: Youngsup
authors.initials: Y
authors.lastname: Song
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis*; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins