Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma.
Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma.
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DOI：
10.1016/j.bone.2016.05.014
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发表时间：
2016-09
期刊：
影响因子：
4.1
通讯作者：
Rubin CT
中科院分区：
文献类型：
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作者：
Pagnotti GM;Chan ME;Adler BJ;Shroyer KR;Rubin J;Bain SD;Rubin CT
骨髓瘤促进骨和骨髓的破坏。由于体力活动有助于肌肉骨骼的保护，我们评估了低强度振动（LIV）（机械信号的一个组成部分）是否可以在骨髓瘤进展期间保护骨骼和骨髓。免疫受损小鼠（n=25）注射人骨髓瘤细胞，而8只（AC）注射盐水。骨髓瘤注射小鼠（LIV; n=13）进行每日机械负荷（15 min/d; 0.3g@90 Hz），而12只（MM）进行假处理。8周时，MM组股骨骨小梁体积（BV）分数比AC组低85%，而LIV仅比AC组低21%，反映出MM组比AC组增加76%。MM组和LIV组皮质BV分别比AC组低21%和15%; LIV显示比MM改善30%。在中轴骨骼中观察到类似的结果，显示与MM相比，MM损失35%，LIV处理的小鼠L5骨保留改善27%。MM中诱导的骨质溶解是AC的9倍，LIV中降低了57%。血清TRACP 5 b，MM比AC高61%，LIV比AC高33%，与MM相比，活性降低45%。骨小梁的组织形态学分析表明MM比AC的侵蚀表面升高70%，而LIV的测量值比MM低58%。MM小鼠股骨中72%的骨髓含有肿瘤，相比之下，LIV的负担降低了31%。MM小鼠（42%）胫骨中出现晚期骨髓坏死，而LIV仅为8%。骨髓瘤浸润与骨质测量呈负相关，而LIV减缓了系统性骨髓瘤相关的骨质下降，并抑制了肿瘤通过后肢的进展。
Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibrations (LIV), a component of mechanical signaling, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n=25) were injected with human-myeloma cells, while 8 (AC) were saline-injected. Myeloma-injected mice (LIV; n=13) were subjected to daily-mechanical loading (15min/d; 0.3g @ 90Hz) while 12 (MM) were sham-handled. At 8w, femurs had 85% less trabecular bone volume (BV) fraction in MM versus AC, yet only a 21% decrease in LIV as compared to as compared to AC, reflecting a 76% increase versus MM. Cortical BV was 21% and 15% lower in MM and LIV, respectively, than AC; LIV showing 30% improvement over MM. Similar outcomes were observed in the axial skeleton, showing a 35% loss in MM with a 27% improved retention of bone in L5 of LIV-treated mice as compared to MM. Transcortical-perforations in the femur from myeloma-induced osteolysis were 9× higher in MM versus AC, reduced by 57% in LIV. Serum-TRACP5b, 61% greater in MM versus AC, rose by 33% in LIV compared to AC, a 45% reduction in activity when compared to MM. Histomorphometric analyses of trabecular bone demonstrated a 70% elevation in eroded surfaces of MM versus AC, while measures in LIV were 58% below those in MM. 72% of marrow in the femur of MM mice contained tumor, contrasted by a 31% lower burden in LIV. MM mice (42%) presented advanced-stage necrosis of marrow in the tibia while present in just 8% of LIV. Myeloma infiltration inversely correlated to measures of bone quality, while LIV slowed systemic myeloma-associated decline in bone quality and inhibited tumor progression through the hindlimbs.