An Early Myeloma Bone Disease Model in Skeletally Mature Mice as a Platform for Biomaterial Characterization of the Extracellular Matrix
An Early Myeloma Bone Disease Model in Skeletally Mature Mice as a Platform for Biomaterial Characterization of the Extracellular Matrix
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骨骼成熟小鼠的早期骨髓瘤骨病模型作为细胞外基质生物材料表征的平台
DOI：
10.1155/2020/3985315
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发表时间：
2020
影响因子：
--
通讯作者：
Jundt F
中科院分区：
文献类型：
--
作者：
Ziouti F;Prates Soares A;Moreno-Jiménez I;Rack A;Bogen B;Cipitria A;Zaslansky P;Jundt F
多发性骨髓瘤(MM)骨病的特征是溶骨性骨组织破坏，导致患者骨痛、骨折、椎体塌陷和脊髓受压。在最初诊断为多发性骨髓瘤时，几乎80%的患者患有骨病。多发性骨髓瘤骨病的早期诊断和干预可能会改善治疗结果和患者存活率。需要新的临床前模型来开发新的骨结构改变的诊断标记物，以便在疾病过程中尽早地进行。在这里，我们报告了一种概念验证、同基因、股内注射MOPC315.BM MM小鼠模型，用于检测和表征注射MM的动物非常早期的细胞外基质(ECM)变化。体内生物发光成像(BLI)证实，在肿瘤细胞接种后21天内，100%具有高破骨细胞活性的动物植入了骨髓瘤。通过高分辨率显微计算机断层扫描(MicroCT)观察到侵袭性骨转换的早期迹象出现在外骨表面。同步辐射相位对比增强微型计算机断层扫描(PCE-CT)显示了非常局部的微结构差异，突出了微米尺度上许多活跃的侵蚀部位和新生骨。相关的背向散射电子成像(BSE)和共聚焦激光扫描显微镜可以直接比较皮质骨中矿化和非矿化的基质变化。21天后，骨细胞陷窝-管状网(OLCN)结构紊乱，骨细胞陷窝呈不规则形。我们的模型为进一步从微观和超微结构水平评估病理性多发性骨髓瘤骨病变的发展提供了潜在的平台。这些有希望的结果使材料科学和药理学研究相结合成为可能，这可能会改善多发性骨髓瘤骨病的早期发现和治疗。
Multiple myeloma (MM) bone disease is characterized by osteolytic bone tissue destruction resulting in bone pain, fractures, vertebral collapse, and spinal cord compression in patients. Upon initial diagnosis of MM, almost 80% of patients suffer from bone disease. Earlier diagnosis and intervention in MM bone disease would potentially improve treatment outcome and patient survival. New preclinical models are needed for developing novel diagnostic markers of bone structural changes as early as possible in the disease course. Here, we report a proof‐of‐concept, syngeneic, intrafemoral MOPC315.BM MM murine model in skeletally mature BALB/c mice for detection and characterization of very early changes in the extracellular matrix (ECM) of MM‐injected animals. Bioluminescence imaging (BLI) in vivo confirmed myeloma engraftment in 100% of the animals with high osteoclast activity within 21 days after tumor cell inoculation. Early signs of aggressive bone turnover were observed on the outer bone surfaces by high‐resolution microcomputed tomography (microCT). Synchrotron phase contrast‐enhanced microcomputer tomography (PCE‐CT) revealed very local microarchitecture differences highlighting numerous active sites of erosion and new bone at the micrometer scale. Correlative backscattered electron imaging (BSE) and confocal laser scanning microscopy allowed direct comparison of mineralized and nonmineralized matrix changes in the cortical bone. The osteocyte lacunar‐canalicular network (OLCN) architecture was disorganized, and irregular‐shaped osteocyte lacunae were observed in MM‐injected bones after 21 days. Our model provides a potential platform to further evaluate pathological MM bone lesion development at the micro‐ and ultrastructural levels. These promising results make it possible to combine material science and pharmacological investigations that may improve early detection and treatment of MM bone disease.
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影响因子：
2.5
作者：
Repp F;Kollmannsberger P;Roschger A;Kerschnitzki M;Berzlanovich A;Gruber GM;Roschger P;Wagermaier W;Weinkamer R
通讯作者：
Weinkamer R
叠层X射线纳米断层扫描量化人类牙本质中的矿物质分布
影响因子：
4.6
作者：
I. Zanette;B. Enders;M. Dierolf;P. Thibault;Regine Gradl;A. Diaz;M. Guizar‐Sicairos;A. Menzel;F. Pfeiffer;P. Zaslansky
通讯作者：
P. Zaslansky
影响因子：
6.2
作者：
Razi, Hajar;Birkhold, Annette I.;Checa, Sara
通讯作者：
Checa, Sara
影响因子：
1.9
作者：
L. F. Bonewald
通讯作者：
L. F. Bonewald
影响因子：
14
作者：
Birkhold, Annette I.;Razi, Hajar;Willie, Bettina M.
通讯作者：
Willie, Bettina M.