Mature Adipocyte-Derived Dedifferentiated Fat Cells Can Trans-Differentiate into Osteoblasts In Vitro and In Vivo only by All-Trans Retinoic Acid
Mature Adipocyte-Derived Dedifferentiated Fat Cells Can Trans-Differentiate into Osteoblasts In Vitro and In Vivo only by All-Trans Retinoic Acid
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DOI：
10.1247/csf.08038
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发表时间：
2008-01-01
影响因子：
1.5
通讯作者：
Kano, Koichiro
中科院分区：
文献类型：
--
作者：
Oki, Yoshinao;Watanabe, Saiko;Kano, Koichiro
我们研究了去分化脂肪（DFAT）细胞，一种成熟的脂肪细胞来源的前脂肪细胞系，是否可以在体外和体内诱导转分化为成骨细胞。全反式维甲酸（RA）诱导DFAT细胞中编码Cbfa 1/Runx 2、osterix、碱性磷酸酶、骨桥蛋白、甲状旁腺激素受体和骨钙素的成骨细胞特异性mRNA表达，但不诱导编码PPAR γ 2、C/EBP α和GLUT 4的脂肪细胞特异性mRNA表达。DFAT细胞表达碱性磷酸酶活性，并在体外对骨基质进行矿化。此外，当DFAT细胞在扩散室中皮下移植到C57 BL/6 N小鼠中时，这些细胞形成异位类骨质组织，而没有任何宿主细胞侵入室。这些结果表明，来自成熟脂肪细胞的DFAT细胞可以在体外和体内使用RA转化为完全分化的成骨细胞。DFAT细胞为研究间充质干细胞衍生的脂肪细胞和成骨细胞的谱系定向提供了独特的模型。确定调节这些过程的途径可能会导致新的治疗策略的发展，以控制骨和脂肪组织的不必要的生长。
We investigated whether de-differentiated fat (DFAT) cells, a mature adipocyte-derived preadipocyte cell line, can be induced to trans-differentiate into osteoblasts in vitro and in vivo. All-trans retinoic acid (RA) induced expression of osteoblast-specific mRNAs encoding Cbfa1/Runx2, osterix, alkaline phosphatase, osteopontin, parathyroid hormone receptor, and osteocalcin in the DFAT cells, but did not induce the expression of adipocyte-specific mRNAs encoding PPAR gamma 2, C/EBP alpha, and GLUT4. Moreover, alkaline phosphatase activity was expressed in DFAT cells and the cells underwent mineralization of the bone matrix in vitro. Furthermore, when DFAT cells were transplanted subcutaneously into C57BL/6N mice in diffusion chambers, these cells formed ectopic osteoid tissue without any host cell-invasion of the chambers. These results indicate that DFAT cells derived from mature adipocytes can be converted into fully differentiated osteoblasts in vitro and in vivo using RA. DFAT cells provide a unique model for studying the lineage commitment of the adipocytes and osteoblasts derived from mesenchymal stem cells. Identification of the pathways that regulate these processes could lead to the development of new therapeutic strategies for control of unwarranted growth of bone and adipose tissue.