Participation of TNF-α in Inhibitory Effects of Adipocytes on Osteoblast Differentiation

Participation of TNF-α in Inhibitory Effects of Adipocytes on Osteoblast Differentiation
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DOI:
10.1002/jcp.25073
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发表时间:
2016-01-01
影响因子:
5.6
通讯作者:
Beloti, Marcio M.
Beloti, Marcio M.
中科院分区:
生物学2区
文献类型:
--
作者:
Abuna, Robrigo P. F.;De Oliveira, Fabiola S.;Beloti, Marcio M.

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骨髓间充质干细胞(BM-MSCs)和脂肪组织间充质干细胞(AT-MSCs)是基于细胞疗法修复骨组织的有吸引力的工具。在这项研究中,我们研究了BM-MSCs和AT-MSCs的成骨和成脂潜能,以及成骨细胞和脂肪细胞之间的串音对细胞表型表达的影响。大鼠BM-MSCs和AT-MSCs分别在生长、成骨或成脂培养基中培养,以评估成骨细胞和脂肪细胞的分化。此外,将成骨细胞与脂肪细胞间接共培养,研究脂肪细胞对成骨细胞分化的影响,反之亦然。在非分化诱导条件下,BM-MSCs和AT-MSCs表现出成骨和成脂潜能。当暴露于成骨培养基时,与AT-MSCs相比,BM-MSCs表现出更高的骨标志物表达。相反,在脂肪生成条件下,与BM-MSCs相比,AT-MSCs显示出更高的脂肪组织标志物表达。脂肪细胞作为间接共培养存在抑制成骨细胞表型的表达,而成骨细胞对脂肪细胞无显著影响。脂肪细胞对成骨细胞的抑制作用是由于脂肪细胞在培养基中释放肿瘤坏死因子α (TNF-)。事实上,在培养基中添加外源性TNF-抑制了BM-MSCs向成骨细胞的分化,模拟了间接共培养效应。总之,我们的研究表明BM-MSCs更具有成骨性,而AT-MSCs更具有成脂性。此外,我们证明了脂肪细胞分泌的TNF-在抑制成骨细胞分化中的关键作用。因此,我们假设BM-MSCs较高的成骨潜能使其成为细胞治疗中诱导骨修复的首选。j .细胞。中国生物医学工程学报,2016,31(2):444 - 444。(c) 2015 Wiley期刊公司
Mesenchymal stem cells from bone marrow (BM-MSCs) and adipose tissue (AT-MSCs) are attractive tools for cell-based therapies to repair bone tissue. In this study, we investigated the osteogenic and adipogenic potential of BM-MSCs and AT-MSCs as well as the effect of crosstalk between osteoblasts and adipocytes on cell phenotype expression. Rat BM-MSCs and AT-MSCs were cultured either in growth, osteogenic, or adipogenic medium to evaluate osteoblast and adipocyte differentiation. Additionally, osteoblasts and adipocytes were indirectly co-cultured to investigate the effect of adipocytes on osteoblast differentiation and vice versa. BM-MSCs and AT-MSCs exhibit osteogenic and adipogenic potential under non-differentiation-inducing conditions. When exposed to osteogenic medium, BM-MSCs exhibited higher expression of bone markers compared with AT-MSCs. Conversely, under adipogenic conditions, AT-MSCs displayed higher expression of adipose tissue markers compared with BM-MSCs. The presence of adipocytes as indirect co-culture repressed the expression of the osteoblast phenotype, whereas osteoblasts did not exert remarkable effect on adipocytes. The inhibitory effect of adipocytes on osteoblasts was due to the release of tumor necrosis factor alpha (TNF-) in culture medium by adipocytes. Indeed, the addition of exogenous TNF- in culture medium repressed the differentiation of BM-MSCs into osteoblasts mimicking the indirect co-culture effect. In conclusion, our study showed that BM-MSCs are more osteogenic while AT-MSCs are more adipogenic. Additionally, we demonstrated the key role of TNF- secreted by adipocytes on the inhibition of osteoblast differentiation. Thus, we postulate that the higher osteogenic potential of BM-MSCs makes them the first choice for inducing bone repair in cell-based therapies. J. Cell. Physiol. 230: 204-214, 2016. (c) 2015 Wiley Periodicals, Inc.