title: Stimulation of osteogenic differentiation in stromal cells of giant cell tumour of bone by zoledronic acid.
abstract: Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations (0 μM, 0.01 μM, 0.1 μM, 1 μM, 5 μM, 30 μM) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1 μM in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.
authors.affiliation: Department of Orthopaedics, Guangzhou Liu Hua Qiao Hospital, Guangzhou, China E-mail : xiaofeizhengcn@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Zheng
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.forename: Qing-Shui
authors.initials: QS
authors.lastname: Yin
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid
chemical_list: D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D050659:Core Binding Factor Alpha 1 Subunit; D004164:Diphosphonates; D007093:Imidazoles; D012333:RNA, Messenger; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; D000077211:Zoledronic Acid