Mesenchymal progenitors in osteopenias of diverse pathologies: differential characteristics in the common shift from osteoblastogenesis to adipogenesis.
Mesenchymal progenitors in osteopenias of diverse pathologies: differential characteristics in the common shift from osteoblastogenesis to adipogenesis.
复制标题
不同病理的骨质减少中的间充质祖细胞：从成骨细胞发生到脂肪发生的共同转变的差异特征
DOI：
10.1038/srep30186
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发表时间：
2016-07-22
影响因子：
4.6
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Sui B;Hu C;Liao L;Chen Y;Zhang X;Fu X;Zheng C;Li M;Wu L;Zhao X;Jin Y
骨质疏松症是由病理因素引起的，如衰老、激素缺乏或过量、炎症和全身性疾病如糖尿病。骨髓基质细胞（BMSCs）是成骨细胞和脂肪细胞的间充质祖细胞，受龛信号调控。在不同的病理状态下，骨髓间充质干细胞的病理特征和功能差异尚不清楚。在此，我们检测了6种骨质疏松模型中，分别由自然衰老、加速衰老（SAMP6）、卵巢切除术（OVX）、1型糖尿病（T1D）、过量糖皮质激素（GIOP）和卵巢切除术（ORX）诱导的骨小梁丢失与骨髓脂肪增加共存。BMSCs的体外特性中，衰老、SAMP6、OVX、GIOP和ORX模型的集落形成率和增殖率均降低。除T1D外，凋亡和细胞衰老均增加，p53和p16表达上调。除GIOP外，成骨作用下降，相应的Runt相关转录因子2（RUNX 2）表达下调。6种脂肪变性模型的脂肪形成增加，相应的过氧化物酶体增殖物激活受体γ（PPARγ）表达上调。这些结果揭示了不同骨质疏松症和性别间BMSCs从成骨细胞向成脂细胞转化的共同特征，为在骨质疏松症的再生治疗中调节驻留BMSCs的功能提供了理论依据。
Osteoporosis is caused by pathologic factors such as aging, hormone deficiency or excess, inflammation, and systemic diseases like diabetes. Bone marrow stromal cells (BMSCs), the mesenchymal progenitors for both osteoblasts and adipocytes, are modulated by niche signals. In differential pathologic states, the pathological characteristics of BMSCs to osteoporoses and functional differences are unknown. Here, we detected that trabecular bone loss co-existed with increased marrow adiposity in 6 osteoporotic models, respectively induced by natural aging, accelerated senescence (SAMP6), ovariectomy (OVX), type 1 diabetes (T1D), excessive glucocorticoids (GIOP) and orchidectomy (ORX). Of the ex vivo characteristics of BMSCs, the colony-forming efficiency and the proliferation rate in aging, SAMP6, OVX, GIOP and ORX models decreased. The apoptosis and cellular senescence increased except in T1D, with up-regulation of p53 and p16 expression. The osteogenesis declined except in GIOP, with corresponding down-regulation of Runt-related transcription factor 2 (RUNX2) expression. The adipogenesis increased in 6 osteoporotic models, with corresponding up-regulation of Peroxisome proliferator activated receptor gamma (PPARγ) expression. These findings revealed differential characteristics of BMSCs in a common shift from osteoblastogenesis to adipogenesis among different osteoporoses and between sexes, and provide theoretical basis for the functional modulation of resident BMSCs in the regenerative therapy for osteoporosis.