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- Title
Technetium-99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor- κB ligand-induced osteoclastogenesis.
- Authors
Gong, Wei; Dou, Huan; Liu, Xianqin; Sun, Lingyun; Hou, Yayi
- Abstract
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-κ B ligand (RANKL)-induced osteoclastogenesis and explored the underlying mechanisms., The murine macrophage cell line RAW264.7 and bone marrow-derived-macrophages from C57 BL/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.
- Subjects
OSTEOCLASTS; TECHNETIUM isotopes; RADIOISOTOPE therapy; NF-kappa B; CARBENES; DIPHOSPHONATES; OSTEOCLAST inhibition
- Publication
Clinical & Experimental Pharmacology & Physiology, 2012, Vol 39, Issue 10, p886
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/j.1440-1681.2012.12006.x