Reversal of loss of bone mass in old mice treated with mefloquine.
Reversal of loss of bone mass in old mice treated with mefloquine.
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DOI：
10.1016/j.bone.2018.06.002
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发表时间：
2018-09
期刊：
影响因子：
4.1
通讯作者：
Plotkin LI
中科院分区：
文献类型：
--
作者：
Pacheco-Costa R;Davis HM;Atkinson EG;Dilley JE;Byiringiro I;Aref MW;Allen MR;Bellido T;Plotkin LI
衰老伴随着不平衡的骨重建、骨细胞凋亡增加以及骨量和机械性能降低;需要改进的药理学方法来对抗随着衰老的骨退化。我们在此研究了甲氟喹（一种用于治疗疟疾和系统性红斑狼疮的药物，可改善糖皮质激素治疗患者的骨丢失）对年轻和老年小鼠骨量和机械性能的影响。年轻的3.5月龄和年老的21月龄雌性C57 BL/6小鼠接受每天5 mg/kg/天的甲氟喹注射，持续14天。老化导致骨体积和机械性能的预期变化。在老年小鼠中，甲氟喹给药逆转了较低的椎骨松质骨体积和骨形成;对皮质骨体积、厚度和转动惯量有适度的影响。甲氟奎给药不会改变循环骨形成标志物P1 NP或碱性磷酸酶的水平，而吸收标志物CTX的水平随着甲氟奎治疗而呈增加趋势。此外，正如预期的那样，与年轻小鼠相比，衰老的骨骼表现出活性半胱天冬酶3表达骨细胞的积累和更高的骨化相关基因的表达，这在两个年龄段都没有被甲氟喹给药改变。在年轻动物中，甲氟喹诱导较高的骨膜骨形成，但较低的皮质内骨形成。此外，与溶剂处理的年轻小鼠相比，甲氟喹处理的小鼠皮质内骨表面上的破骨细胞数量更高，循环中的CTX水平增加。与此相一致的是，将甲氟喹添加到从年轻小鼠分离的骨髓细胞中，导致体外破骨细胞基因表达增加和破骨细胞数量增加的趋势。总之，我们的研究结果确定了甲氟喹的年龄和骨骼部位特异性骨骼效应。此外，我们的研究结果强调了甲氟喹给药对老年动物椎体松质骨质量的有益作用，提高了使用这种药理学抑制剂来保护骨骼健康的可能性。
Aging is accompanied by imbalanced bone remodeling, elevated osteocyte apoptosis, and decreased bone mass and mechanical properties; and improved pharmacologic approaches to counteract bone deterioration with aging are needed. We examined herein the effect of mefloquine, a drug used to treat malaria and systemic lupus erythematosus and shown to ameliorate bone loss in glucocorticoid-treated patients, on bone mass and mechanical properties in young and old mice. Young 3.5-month-old and old 21-month-old female C57BL/6 mice received daily injections of 5mg/kg/day mefloquine for 14 days. Aging resulted in the expected changes in bone volume and mechanical properties. In old mice mefloquine administration reversed the lower vertebral cancellous bone volume and bone formation; and had modest effects on cortical bone volume, thickness, and moment of inertia. Mefloquine administration did not change the levels of the circulating bone formation markers P1NP or alkaline phosphatase, whereas levels of the resorption marker CTX showed trends towards increase with mefloquine treatment. In addition, and as expected, aging bones exhibited an accumulation of active caspase3-expressing osteocytes and higher expression of apoptosis-related genes compared to young mice, which were not altered by mefloquine administration at either age. In young animals, mefloquine induced higher periosteal bone formation, but lower endocortical bone formation. Further, osteoclast numbers were higher on the endocortical bone surface and circulating CTX levels were increased, in mefloquine-compared to vehicle-treated young mice. Consistent with this, addition of mefloquine to bone marrow cells isolated from young mice led to increased osteoclastic gene expression and a tendency towards increased osteoclast numbers in vitro. Taken together our findings identify the age and bone-site specific skeletal effects of mefloquine. Further, our results highlight a beneficial effect of mefloquine administration on vertebral cancellous bone mass in old animals, raising the possibility of using this pharmacologic inhibitor to preserve skeletal health with aging.
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影响因子：
7.8
作者：
Davis HM;Pacheco-Costa R;Atkinson EG;Brun LR;Gortazar AR;Harris J;Hiasa M;Bolarinwa SA;Yoneda T;Ivan M;Bruzzaniti A;Bellido T;Plotkin LI
通讯作者：
Plotkin LI
DOI：
10.1002/jbmr.2740
发表时间：
2016-04
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Cheung WY;Fritton JC;Morgan SA;Seref-Ferlengez Z;Basta-Pljakic J;Thi MM;Suadicani SO;Spray DC;Majeska RJ;Schaffler MB
通讯作者：
Schaffler MB
影响因子：
7.3
作者：
Gribble, FM;Davis, TME;Ashcroft, FM
通讯作者：
Ashcroft, FM
影响因子：
7.3
作者：
Coker, SJ;Batey, AJ;Eisner, DA
通讯作者：
Eisner, DA
DOI：
10.1073/pnas.0402044101
发表时间：
2004-08-17
影响因子：
11.1
作者：
Cruikshank, SJ;Hopperstadt, M;Srinivas, M
通讯作者：
Srinivas, M