Rummler Maximilian, Ziouti Fani, Bouchard Alice L, Brandl Andreas, Duda Georg N, Bogen Bjarne, Beilhack Andreas, Lynch Maureen E, Jundt Franziska, Willie Bettina M
Research Centre, Shriners Hospital for Children-Canada, Montreal, Canada; Julius Wolff Institute and Berlin-Brandenburg Center for Regenerative Therapies, Charité Universitätsmedizin Berlin, Berlin, Germany; Department of Pediatric Surgery, McGill University, Montreal, Canada.
Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Acta Biomater. 2021 Jan 1;119:247-258. doi: 10.1016/j.actbio.2020.10.041. Epub 2020 Oct 29.
Bone continually adapts to changing external loading conditions via (re)modeling (modeling and remodeling) processes. While physical activity is known to beneficially enhance bone mass in healthy individuals, little is known in how physical stimuli affect osteolytic bone destruction in patients suffering from multiple myeloma bone disease. Multiple myeloma (MM) is caused by malignant plasma cells in the bone marrow, shifting the balance in bone remodeling towards massive resorption. We hypothesized that in vivo tibial mechanical loading has anabolic effects in mice with locally injected MOPC315.BM.Luc cells. Conventional microCT analysis revealed enhanced cortical bone mass and microstructure in loaded compared to nonloaded mice. State-of-the-art time-lapse microCT based image analysis demonstrated bone (re)modeling processes at the endosteal and periosteal surfaces as the underlying causes of increased bone mass. Loading prevented the progression and development of osteolytic destruction. Physical stimuli also diminished local MM cell growth and dissemination evidenced by quantification of MM cell-specific immunoglobulin A levels in the serum of mice and by bioluminescence analysis. These data indicate that mechanical loading not only rescues the bone phenotype, but also exerts cell-extrinsic anti-myeloma effects in the MOPC315.BM.Luc model. In conclusion, the use of physical stimuli should be further investigated as an anabolic treatment for osteolytic bone destruction in patients with MM.
骨骼通过（再）建模（建模和重塑）过程持续适应不断变化的外部负荷条件。虽然已知体育活动能有益地增加健康个体的骨量，但对于物理刺激如何影响多发性骨髓瘤骨病患者的溶骨性骨破坏却知之甚少。多发性骨髓瘤（MM）由骨髓中的恶性浆细胞引起，使骨重塑的平衡向大量吸收方向转变。我们假设，在局部注射MOPC315.BM.Luc细胞的小鼠中，体内胫骨机械负荷具有合成代谢作用。传统的显微CT分析显示，与未加载的小鼠相比，加载小鼠的皮质骨量和微观结构增强。基于先进的延时显微CT图像分析表明，骨内膜和骨膜表面的骨（再）建模过程是骨量增加的根本原因。加载阻止了溶骨性破坏的进展和发展。通过对小鼠血清中MM细胞特异性免疫球蛋白A水平的定量分析和生物发光分析证明，物理刺激还减少了局部MM细胞的生长和扩散。这些数据表明，机械负荷不仅能挽救骨表型，而且在MOPC315.BM.Luc模型中还具有细胞外抗骨髓瘤作用。总之，应进一步研究将物理刺激作为MM患者溶骨性骨破坏的合成代谢治疗方法。
