Technetium-99 conjugated with methylene diphosphonate ameliorates ovariectomy-induced osteoporotic phenotype without causing osteonecrosis in the jaw.
Technetium-99 conjugated with methylene diphosphonate ameliorates ovariectomy-induced osteoporotic phenotype without causing osteonecrosis in the jaw.
复制标题
DOI：
10.1007/s00223-012-9649-7
复制
发表时间：
2012-12
影响因子：
4.2
通讯作者：
Shi, Songtao
中科院分区：
文献类型：
--
作者：
Zhao, Yinghua;Wang, Lei;Liu, Yi;Akiyama, Kentaro;Chen, Chider;Atsuta, Ikiru;Zhou, Tao;Duan, Xiaohong;Jin, Yan;Shi, Songtao
关键词：
锝-99偶联二膦酸亚甲基（99Tc-MDP）是一种新型的无放射性二膦酸衍生物，多年来在国内已成功用于治疗关节炎。由于双膦酸盐治疗有可能诱导双膦酸盐相关的颌骨骨坏死（BRONJ），我们研究99Tc-MDP是否代表了一种新的双膦酸盐抗吸收治疗，以改善雌激素缺乏诱导的骨吸收，同时降低引起BRONJ的风险。我们发现，与未治疗的OVX组相比，99tc - mdp处理的卵巢切除（OVX）小鼠通过抑制破骨细胞和增强骨髓间充质干细胞（BMMSCs）的成骨分化，显著改善了骨密度（BMD）和小梁骨体积。为了确定诱导BRONJ的潜力，我们通过尾静脉给药99Tc-MDP/地塞米松（Dex）或唑来膦酸钠/Dex，然后拔除上颌第一磨牙。有趣的是，与唑来膦酸钠治疗组相比，99Tc-MDP治疗在上颌骨诱导骨坏死的风险更低，部分原因是99Tc-MDP既没有抑制适应性调节性T细胞（Tregs），也没有激活炎症性T辅助产生白细胞介素17细胞（Th17）。综上所述，我们的研究结果表明，99Tc-MDP治疗骨质疏松症可能是一种有希望的治疗方法，其引起BRONJ的风险较低。
Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) is a novel bisphosphonate derivative without radioactivity and has been successfully used to treat arthritis in China for years. Since bisphosphonate therapy has the potential to induce bisphosphonate-associated osteonecrosis of the jaw (BRONJ), we examine whether 99Tc-MDP represents a new class of bisphosphonate for anti-resorptive therapy to ameliorate estrogen deficiency–induced bone resorption with less risk of causing BRONJ. We showed that 99Tc-MDP-treated ovariectomized (OVX) mice had significantly improved bone mineral density (BMD) and trabecular bone volume in comparison to the untreated OVX group by inhibiting osteoclasts and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). To determine the potential of inducing BRONJ, 99Tc-MDP/dexamethasone (Dex) or zoledronate/Dex were administered into C57BL/6J mice via the tail vein, followed by extraction of maxillary first molars. Interestingly, 99Tc-MDP treatment showed less risk to induce osteonecrosis in the maxillary bones compared to zoledronate treatment group, partially because 99Tc-MDP neither suppressed adaptive regulatory T cells (Tregs) nor activated the inflammatory T-helper-producing interleukin 17 cells (Th17). Taken together, our findings demonstrate that 99Tc-MDP therapy may be a promising approach in the treatment of osteoporosis with less risk of causing BRONJ.
登录
查看更多内容
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
5
作者：
Kovacic, Natasa;Grcevic, Danka;Marusic, Ana
通讯作者：
Marusic, Ana
DOI：
10.1073/pnas.251534698
发表时间：
2001-11-20
影响因子：
11.1
作者：
Roggia, C;Gao, YH;Pacifici, R
通讯作者：
Pacifici, R
影响因子：
4.4
作者：
Lai, Kunbei;Xu, Li;Ye, Haiyun
通讯作者：
Ye, Haiyun
影响因子：
15.9
作者：
Miura, M;Chen, XD;Shi, ST
通讯作者：
Shi, ST