Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice.
Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice.
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DOI：
10.1016/j.bonr.2014.12.002
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发表时间：
2015-06
期刊：
影响因子：
2.5
通讯作者：
Tanaka S
中科院分区：
文献类型：
--
作者：
Tokuyama N;Hirose J;Omata Y;Yasui T;Izawa N;Matsumoto T;Masuda H;Ohmiya T;Yasuda H;Saito T;Kadono Y;Tanaka S
我们在卵巢切除小鼠中检查了特立哌酮和抗RANKL（核因子κB配体受体激活剂）单克隆抗体的单独和联合作用。对三个月大的雌性C57 BL/6小鼠进行卵巢切除（OVX）或假手术。OVX后4周，他们被分配到3个不同的组，单独接受抗RANKL单克隆抗体（Ab）（OVX后4周单次注射5 mg/kg，Ab组），单独接受特立帕鲁肽（从OVX后4周开始，每天注射80 μg/kg，持续4周，PTH组），或mAb+特立帕鲁肽（Ab + PTH组）。OVX后8周处死小鼠。测量股骨和腰椎的骨密度（BMD）。后肢进行组织学和组织形态学分析。测定血清骨钙素和CTX-Ⅰ水平，观察骨转换情况。与Ab组相比，Ab + PTH组股骨远端和股骨干BMD明显增加。与Ab组相比，PTH组和Ab + PTH组皮质骨体积显著增加。Ab + PTH组骨转换抑制程度与Ab组相同。Ab组和Ab + PTH组TRAP阳性多核细胞数量明显减少。这些结果表明，与单独给药相比，特立哌齐与抗RANKL抗体联合给药对OVX小鼠的BMD具有累加效应。研究了抗RANKL抗体和特立帕肽在卵巢切除小鼠中的作用。抗RANKL抗体和特立帕肽增加了不同区域的骨量。抗RANKL抗体和特立帕鲁肽的组合具有累加效应。Teriparitide，而不是抗RANKL抗体，增加骨膜骨形成。
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. The effects of anti-RANKL antibody and teriparitide in ovariectomized mice was studied. Anti-RANKL antibody and teriparatide increased bone mass at the distinct regions. Combination of anti-RANKL antibody and teriparatide had additive effects. Teriparitide, but not anti-RANKL antibody, increased periosteal bone formation.