Bone formation induced by BMP-2 in human osteosarcoma cells.
Bone formation induced by BMP-2 in human osteosarcoma cells.
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DOI：
10.3892/ijo.2013.2030
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发表时间：
2013-10
影响因子：
5.2
通讯作者：
Lin CY
中科院分区：
文献类型：
--
作者：
Wang L;Park P;La Marca F;Than K;Rahman S;Lin CY
我们以前的研究表明，BMP-2抑制肿瘤干细胞的致瘤性，所述肿瘤干细胞被鉴定为来自人骨肉瘤细胞系OS 99 -1的具有高醛脱氢酶活性的细胞（ALDH br细胞）。我们进一步研究了BMP-2是否能够在OS 99 -1细胞中诱导骨形成。使用流式细胞术分选来分离致瘤性ALDH br和非致瘤性ALDH lo细胞。qRT-PCR用于定量基因表达。异种移植模型用于验证骨形成 in vivo . ALDH lo细胞中BMPR 1B和BMPR 2的mRNA表达量显著高于ALDH br细胞，其中ALDH lo细胞中BMPR 1B的表达量是ALDH br细胞的1.8倍。还发现BMP-2在ALDH lo细胞中诱导比ALDH br细胞更高的成骨标志物Runx-2、Osterix（Osx）、碱性磷酸酶（ALP）和I型胶原的转录，其由经典Smad信号传导途径介导。 在体内，BMP-2被鉴定为在ALDH br和ALDH lo细胞中诱导骨形成。所有接受1× 104 ALDH lo细胞的动物均用30 在小鼠中注射后1-2周内，每只动物μ g BMP-2显示骨形成。BMP-2诱导ALDH lo细胞成骨的骨矿物质含量显著高于ALDH br细胞。BMP-2在异种骨肉瘤细胞中诱导骨形成，并且BMP-2可能通过诱导分化沿着成骨途径对治疗人骨肉瘤具有有希望的治疗作用。
Our previous studies demonstrated that BMP-2 inhibits the tumorigenicity of cancer stem cells identified as cells with high aldehyde dehydrogenase activity (ALDH br cells) from the human osteosarcoma cell line OS99-1. We further investigated whether BMP-2 is capable of inducing bone formation in OS99-1 cells. Flow cytometry sorting was used to isolate tumorigenic ALDH br and non-tumorigenic ALDH lo cells. qRT-PCR was used to quantify the gene expression. A xenograft model was used to verify the bone formation in vivo . There was significantly higher mRNA expression of BMPR1B and BMPR2 in ALDH lo cells compared with that in ALDH br cells and the BMPR1B expression in ALDH lo cells was ∼8-fold higher compared to that in ALDH br cells. BMP-2 was also found to induce higher transcription of osteogenic markers Runx-2, Osterix (Osx), alkaline phosphatase (ALP) and collagen type I in ALDH lo cells compared to ALDH br cells, which were mediated by the canonical Smad signaling pathway. In vivo , BMP-2 was identified to induce bone formation in both ALDH br and ALDH lo cells. All animals receiving 1×10 4 ALDH lo cells treated with 30 μ g of BMP-2 per animal showed bone formation within 1–2 weeks after injection in mice. Bone formation induced by BMP-2 in ALDH lo cells showed significantly more bone mineral content compared to that in ALDH br cells. BMP-2 induces bone formation in heterogeneous osteosarcoma cells and BMP-2 may have a promising therapeutic role for treating human osteosarcoma by inducing differentiation along an osteogenic pathway.
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影响因子：
--
作者：
Barboza, E;Caula, A;Machado, F
通讯作者：
Machado, F
影响因子：
4
作者：
Brubaker, KD;Corey, E;Vessella, RL
通讯作者：
Vessella, RL
影响因子：
4.7
作者：
Langenfeld, EM;Calvano, SE;Langenfeld, J
通讯作者：
Langenfeld, J
影响因子：
3.8
作者：
Arnold, SF;Tims, E;McGrath, BE
通讯作者：
McGrath, BE
DOI：
10.1186/1756-9966-29-85
发表时间：
2010-06-30
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Ma Y;Ma L;Guo Q;Zhang S
通讯作者：
Zhang S