Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal.
Direct phenotypic conversion of human fibroblasts into functional osteoblasts triggered by a blockade of the transforming growth factor-β signal.
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DOI：
10.1038/s41598-018-26745-2
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发表时间：
2018-05-31
影响因子：
4.6
通讯作者：
Mazda O
中科院分区：
文献类型：
--
作者：
Yamamoto K;Kishida T;Nakai K;Sato Y;Kotani SI;Nishizawa Y;Yamamoto T;Kanamura N;Mazda O
从人体细胞中产生功能性成骨细胞的过程可能为骨骼疾病的新型有效移植治疗铺平道路。在这里，我们报告了人成纤维细胞诱导成骨细胞表型培养与ALK 5 i II，这是一种特异性抑制剂激活素样激酶5（ALK 5）（肿瘤生长因子-β受体1（TGF-β R1））。用ALK 5 i II培养的细胞表达成骨细胞特异性基因并大量产生钙化骨基质，类似于从间充质干细胞（MSC-OBs）诱导的成骨细胞。除了ALK 5 i II之外，用维生素D3处理诱导更多的成骨细胞样特征，并且转化效率达到约90%。化学化合物介导的直接转化成骨细胞（cOBs）在成骨细胞相关基因的表达谱方面与人原代成骨细胞相似。cOBs在体内大量产生骨基质，并在移植到免疫缺陷小鼠的人工诱导的股骨缺损处后促进骨愈合。本方法实现了人成纤维细胞高效、无转基因、高功能成骨细胞的直接转化，为骨再生治疗提供了新的思路。
A procedure to generate functional osteoblasts from human somatic cells may pave the way to a novel and effective transplantation therapy in bone disorders. Here, we report that human fibroblasts were induced to show osteoblast phenotypes by culturing with ALK5 i II, which is a specific inhibitor for activin-like kinase 5 (ALK5) (tumor growth factor-β receptor 1 (TGF-β R1)). Cells cultured with ALK5 i II expressed osteoblast-specific genes and massively produced calcified bone matrix, similar to the osteoblasts induced from mesenchymal stem cells (MSC-OBs). Treatment with vitamin D3 in addition to ALK5 i II induced more osteoblast-like characters, and the efficiency of the conversion reached approximately 90%. The chemical compound-mediated directly converted osteoblasts (cOBs) were similar to human primary osteoblasts in terms of expression profiles of osteoblast-related genes. The cOBs abundantly produced bone matrix in vivo and facilitated bone healing after they were transplanted into immunodeficient mice at an artificially induced defect lesion in femoral bone. The present procedure realizes a highly efficient direct conversion of human fibroblasts into transgene-free and highly functional osteoblasts, which might be applied in a novel strategy of bone regeneration therapy in bone diseases.
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影响因子：
48
作者：
Lin, Tongxiang;Ambasudhan, Rajesh;Yuan, Xu;Li, Wenlin;Hilcove, Simon;Abujarour, Ramzey;Lin, Xiangyi;Hahm, Heung Sik;Hao, Ergeng;Hayek, Alberto;Ding, Sheng
通讯作者：
Ding, Sheng
TGF-β对牙周韧带细胞对硬组织形成细胞的早期承诺负面调节。
影响因子：
3.7
作者：
Kawahara T;Yamashita M;Ikegami K;Nakamura T;Yanagita M;Yamada S;Kitamura M;Murakami S
通讯作者：
Murakami S
影响因子：
3.8
作者：
Qiao, Ling Juan;Kang, Kyung Lhi;Heo, Jung Sun
通讯作者：
Heo, Jung Sun
影响因子：
7.7
作者：
Rena, G;Bain, J;Cohen, P
通讯作者：
Cohen, P
影响因子：
7.3
作者：
Gellibert, FO;Woolven, J;Hartley, D
通讯作者：
Hartley, D