title: Smad3 is the key to transforming growth factor-β1-induced osteoclast differentiation in giant cell tumor of bone.
abstract: Giant cell tumor (GCT) of bone is a benign but locally aggressive neoplasm of bone. However, molecular mechanisms underlying osteolysis in GCT have not been deeply understood. The aim of this study was to investigate one of the possible mechanisms underlying the up-regulation of receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) expression. First, we performed an immunohistochemical study on transforming growth factor-β1 (TGF-β1) expression in 83 cases with GCT and found that increased TGF-β1 staining was significantly correlated with Campanacci stages(Spearman's correlation = 0.335, p = 0.002). Next, we investigated the mechanism of the effect of TGF-β1 on osteolysis of GCT and examined the effects of TGF-β1 plus or minus specific inhibitor of Smad3 (SIS3) on the expression of RANKL/OPG ratio at the mRNA and protein levels in two primary GCT cell lines. The results clearly indicated that TGF-β1 is capable of significantly increasing RANKL/OPG ratio (p GCT1 = 0.000, p GCT2 = 0.000) and that SIS3 is capable of reversing the ratio, suggesting that Smad3 is the key to TGF-β1-induced increased the ratio. In the co-culture system, we found that SIS3 reversed the effects of TGF-β1-induced osteoclast formation in the co-culture system (p GCT1 = 0.000, p GCT2 = 0.000). Our findings indicate that TGF-β1 plays an important role in the osteolysis of GCT via Smad3.
authors.affiliation: Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, People's Republic of China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Lou
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Tingting
authors.initials: T
authors.lastname: Ren
authors.forename: Shun
authors.initials: S
authors.lastname: Tang
authors.forename: Xianbo
authors.initials: X
authors.lastname: Peng
authors.forename: Qunshan
authors.initials: Q
authors.lastname: Lu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D010010:Osteoclasts / Q000473:pathology*; D010014:Osteolysis / Q000235:genetics / Q000473:pathology; D053244:Osteoprotegerin / Q000235:genetics; D053245:RANK Ligand / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C505688:TNFSF11 protein, human; D053773:Transforming Growth Factor beta1