Tonsil-Derived Mesenchymal Stem Cells Promote Bone Mineralization and Reduce Marrow and Visceral Adiposity in a Mouse Model of Senile Osteoporosis
Tonsil-Derived Mesenchymal Stem Cells Promote Bone Mineralization and Reduce Marrow and Visceral Adiposity in a Mouse Model of Senile Osteoporosis
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DOI：
10.1089/scd.2016.0063
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发表时间：
2016-08-01
影响因子：
4
通讯作者：
Ryu, Kyung-Ha
中科院分区：
文献类型：
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作者：
Kim, Yu-Hee;Park, Minhwa;Ryu, Kyung-Ha
骨质疏松症是一种影响 65 岁以上 35% 女性和 20% 男性的疾病。骨形成减少和骨吸收增加是导致骨质疏松症的已知因素，但最近的研究表明骨髓脂肪组织 (MAT) 与骨质疏松症之间呈正相关。此前，我们观察到扁桃体来源的间充质干细胞（T-MSC）在骨髓耗竭小鼠模型中减少了 MAT。这促使我们研究老年骨质疏松症，以表征 T-MSC 的骨形成作用以及 MAT 减少作用。在衰老加速小鼠pron 6 (SAMP6) 小鼠模型中，我们通过尾静脉注射T-MSC 或T-MSC 条件培养基(CM)，并使用显微CT 扫描和苏木精和伊红(H&E) 染色检查骨微结构的变化。通过 ELISA 检测骨质疏松症的生化标志物、脱氧吡啶啉 (DPD) 和骨钙素。结果表明，骨质疏松症的进展在一定程度上是通过维持骨钙素的产生和阻止 MAT 的积累来减缓的。通过 T-MSC CM 处理，体外培养小鼠前成骨细胞系，测定基质矿化的增加。有趣的是，T-MSC CM 诱导持续体重减轻并选择性减少内脏脂肪组织质量。最后，在体外测定了 T-MSC CM 的抗脂肪形成作用。总之，骨调节与 MAT 结合可被视为治疗老年骨质疏松症的新治疗选择，该报告可能为未来使用 T-MSC 进行细胞治疗提供框架。
Osteoporosis is a disease that affects 35% women and 20% men aged more than 65 years. Reduction in bone formation and increased bone resorption are known factors that drive osteoporosis, but recent studies suggest a positive correlation between bone marrow adipose tissue (MAT) and osteoporosis. Previously, we have observed that tonsil-derived mesenchymal stem cells (T-MSCs) reduce MAT in a mouse model of bone marrow depletion. That prompted us to investigate on the senile osteoporosis to characterize the bone-forming effect, as well as MAT-reducing effect of T-MSCs. In a mouse model of senescence-accelerated mouse prone 6 (SAMP6), we injected T-MSCs or T-MSC conditioned medium (CM) through tail vein and examined changes in bone microstructure using micro-CT scan and hematoxylin & eosin (H&E) staining. Biochemical markers of osteoporosis, deoxypyridinoline (DPD) and osteocalcin, were examined by ELISA. Results demonstrated attenuation in the progression of osteoporosis, in part, by sustaining osteocalcin production and by blocking MAT accumulation. Increase in matrix mineralization was determined using in vitro culture of murine preosteoblast cell line by treatment of T-MSC CM. Interestingly, T-MSC CM induced continuous weight loss and selectively reduced visceral adipose tissue mass. Finally, antiadipogenic effects of T-MSC CM were determined in vitro. In conclusion, regulation of bone together with MAT could be considered as a new therapeutic option for the treatment of senile osteoporosis and this report may provide a framework for future cell therapy using T-MSCs.