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抗RANKL单克隆抗体与特立帕肽对去卵巢小鼠的单独及联合作用

Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice.

作者信息

Tokuyama Naoto, Hirose Jun, Omata Yasunori, Yasui Tetsuro, Izawa Naohiro, Matsumoto Takumi, Masuda Hironari, Ohmiya Toshinobu, Yasuda Hisataka, Saito Taku, Kadono Yuho, Tanaka Sakae

机构信息

Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655,Japan.

Bioindustry Division, Oriental Yeast Co., Ltd., Azusawa 3-6-10, Itabashi-ku, Tokyo 174-8505, Japan.

出版信息

Bone Rep. 2015 Jan 21;2:1-7. doi: 10.1016/j.bonr.2014.12.002. eCollection 2015 Jun.

Abstract

We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand) monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX) or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab) alone (5 mg/kg single injection at 4 weeks after OVX, Ab group), teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group), or mAb plus teriparatide (Ab + PTH group). Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD) was measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis. Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group, Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.

摘要

我们研究了特立帕肽和抗RANKL(核因子κB受体激活剂配体)单克隆抗体对去卵巢小鼠的单独及联合作用。将3月龄雌性C57BL/6小鼠进行去卵巢手术(OVX)或假手术。OVX术后4周,将它们分为3个不同组,分别单独接受抗RANKL单克隆抗体(Ab)(OVX术后4周单次注射5mg/kg,Ab组)、单独接受特立帕肽(OVX术后4周起每天注射80μg/kg,共4周,PTH组)或单克隆抗体加特立帕肽(Ab + PTH组)。OVX术后8周处死小鼠。测量股骨和腰椎的骨密度(BMD)。对后肢进行组织学和组织形态计量学分析。检测血清骨钙素和CTX-I水平以研究骨转换。与Ab组相比,Ab + PTH组股骨远端和股骨干的BMD显著增加。与Ab组相比,PTH组和Ab + PTH组的皮质骨体积显著增加。Ab + PTH组的骨转换被抑制到与Ab组相同的程度。Ab组和Ab + PTH组中TRAP阳性多核细胞的数量明显减少。这些结果表明,与单独治疗相比,特立帕肽与抗RANKL抗体联合治疗对去卵巢小鼠的骨密度有相加作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a146/5365172/43686429ee45/gr1.jpg

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