The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats
The novel bisphosphonate disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate increases bone mass in post-ovariectomy rats
复制标题
新型双膦酸二氢二钠-4-[(甲硫基)苯硫基]甲烷双膦酸盐可增加卵巢切除术后大鼠的骨量
DOI：
10.1016/j.jphs.2016.04.011
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发表时间：
2016
影响因子：
3.5
通讯作者：
Kaoru Igarashi
中科院分区：
文献类型：
--
作者：
Aiko Takizawa;Mirei Chiba;Takeru Ota;Mayumi Yasuda;Keiko Suzuki;Takuya Kanemitsu;Takashi Itoh;Hisashi Shinoda;Kaoru Igarashi
新型双膦酸盐（BP）二氢二钠-4-[（甲基硫）苯基硫]甲烷双膦酸盐（MPMBP）是一种不含氮的BP，具有抗氧化侧链，具有抗炎特性。我们研究了该化合物对成年大鼠卵巢切除术（OVX）所致骨质流失的全身作用。显微计算机断层扫描显示，MPMBP增加了干骺端和骨干的骨量和骨密度，改善了骨质疏松骨的机械强度。四环素和钙黄蛋白连续骨标记表明，MPMBP降低了原发性海绵的纵向生长，但刺激了骨干皮质骨的形成。MPMBP增加了PS中I型胶原的积累，减少了骨髓中脂肪细胞的数量和大小，提示OVX诱导的骨髓脂肪生成增加有抑制作用。此外，MPMBP减少了OVX诱导的骨吸收组织蛋白酶k阳性破骨细胞的数量。提示MPMBP可改善雌激素缺乏所致骨质流失。刺激骨形成和抑制骨吸收可能在MPMBP治疗后骨量和骨密度的增加中发挥作用。
The novel bisphosphonate (BP) disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate (MPMBP) is a non-nitrogen-containing BP with an antioxidant side chain that possesses anti-inflammatory properties. We investigated the systemic effects of this compound on bone loss induced by ovariectomy (OVX) in adult rats. Micro-computed tomography revealed that MPMBP increased bone mass and density in both the metaphysis and diaphysis, and improved the structural properties important for mechanical strength of osteoporotic bone. Sequential bone labeling with tetracycline and calcein indicated that MPMBP decreased longitudinal growth of the primary spongiosa (PS), but stimulated cortical bone formation in the diaphysis. MPMBP increased type I collagen accumulation in the PS, and decreased the number and size of adipocytes in the bone marrow, suggesting inhibition of increased bone marrow adipogenesis induced by OVX. Furthermore, MPMBP reduced the number of bone resorbing cathepsin K-positive osteoclasts induced by OVX. These results suggest that MPMBP could improve bone loss induced by estrogen deficiency. Both stimulation of bone formation and inhibition of bone resorption might play a role in the increase in bone mass and bone density after MPMBP treatment.