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Technetium-99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis.
MedLine Citation:
PMID:  23013134     Owner:  NLM     Status:  In-Data-Review    
In the present study, we investigated the effects of technetium-99 conjugated with methylene diphosphonate ((99) Tc-MDP), an agent used in radionuclide therapy, on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and explored the underlying mechanisms. The murine macrophage cell line RAW264.7 and bone marrow-derived-macrophages from C57BL/6 mice (BMM) were used as models for osteoclastogenesis in vitro. The expression of some key factors in RANKL (50 ng/mL)-induced osteoclastogenesis in RAW264.7 cells was investigated by flow cytometry and real-time reverse transcription-polymerase chain reaction (RT-PCR). To detect multinucleated osteoclast formation, RAW264.7 cells were induced with RANKL for 4 days, whereas BMM were induced by 50 ng/mL RANKL and 20 ng/mL macrophage colony-stimulating factor for 7 days, before being stained with tartrate-resistant acid phosphatase. Osteoclastogenesis was evaluated using the osteoclast markers CD51, matrix metalloproteinase (MMP)-9 and cathepsin K. At 0.01 μg/mL, (99) Tc-MDP significantly inhibited RANKL-induced osteoclastogenesis without any cytotoxicity. In addition, (99) Tc-MDP abolished the appearance of multinucleated osteoclasts. Real-time RT-PCR analysis of transcription factor expression revealed that (99) Tc-MDP inhibited the expression of c-Fos and nuclear factor of activated T cells. In addition, (99) Tc-MDP inhibited the expression of the inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. Finally, (99) Tc-MDP inhibited the activation of mitogen-activated protein kinases in RAW264.7 cells following RANKL stimulation. In conclusion, (99) Tc-MDP possesses anti-osteoclastogenic activity against RANKL-induced osteoclast formation.
Wei Gong; Huan Dou; Xianqin Liu; Lingyun Sun; Yayi Hou
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  39     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  886-93     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.
Immunology and Reproductive Biology Laboratory, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
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