LIM domain protein-3 (LMP3) cooperates with BMP7 to promote tissue regeneration by ligament progenitor cells.

LIM domain protein-3 (LMP3) cooperates with BMP7 to promote tissue regeneration by ligament progenitor cells.
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DOI:
10.1038/gt.2011.203
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发表时间:
2013-01
期刊:
影响因子:
5.1
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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骨髓间充质干细胞(MSCs)的成骨关键调控因子的基因转移是一种很有前途的骨再生策略。LMP3是LIM结构域矿化蛋白(LMP)的转录变异体,缺乏LIM结构域,已有报道在体内外均能诱导成骨。由于目前对LMP3基因治疗对牙周膜细胞成骨分化的影响知之甚少,本研究试图探讨LMP3基因治疗是否能促进牙周膜细胞的矿化和成骨。我们的结果表明,腺病毒介导的LMP3(AdLMP3)基因转移显著上调了人PDL中ALP、BSP和BMP2基因的表达,并增加了体外培养的人PDL的基质矿化。虽然AdLMP3基因转导PDL细胞不能在体内诱导异位成骨,但我们发现AdLMP3促进了新骨形成,并与AdBMP7基因共转导。我们的研究提供了LMP3和BMP-7在体内存在协同作用的证据,提示LMP3的传递可能被用于增强BMP介导的成骨。LMP3和BMP-7联合基因治疗也可能在口腔和牙周再生医学中有特定的应用。
Gene transfer of key regulators of osteogenesis for mesenchymal stem cells (MSCs) represents a promising strategy to regenerate bone. It has been reported that LMP3, a transcription variant of LIM domain mineralization protein (LMP) lacking LIM domains, can induce osteogenesis in vitro and in vivo. Since little is known about the effects of LMP3 gene therapy on periodontal ligament (PDL) cell osteogenic differentiation, this study sought to explore whether gene delivery of LMP3 can promote PDL cell mineralization and bone formation. Our results showed that adenoviral mediated gene transfer of LMP3 (AdLMP3) significantly upregulated ALP, BSP, and BMP2 gene expression and increased in vitro matrix mineralization in human PDL. Although AdLMP3 gene delivery to PDL cells did not induce ectopic bone formation in vivo, we found that AdLMP3 augments new bone formation, which co-delivered with AdBMP7 gene transfer. Our study provides evidence that there is a synergistic effect between LMP3 and BMP-7 in vivo, suggesting that LMP3 delivery may be used to augment BMP-mediated osteogenesis. LMP3 and BMP-7 combinatory gene therapy may also have specific applications for oral and periodontal regenerative medicine.
DOI: 10.1016/j.bone.2010.03.013
发表时间: 2010-07
期刊: BONE
影响因子: 4.1
作者:
Lin, Zhao;Navarro, Valeria Pontelli;Kempeinen, Kathryn M.;Franco, Leo M.;Jin, Qiming;Sugai, James V.;Giannobile, William V.
通讯作者: Giannobile, William V.
DOI: 10.1038/sj.gt.3302207
发表时间: 2004-04-01
期刊: GENE THERAPY
影响因子: 5.1
作者:
Pola, E;Gao, W;Robbins, P
通讯作者: Robbins, P
DOI: 10.1902/jop.2004.75.1.154
发表时间: 2004-01-01
影响因子: 4.3
作者:
Zhao, M;Jin, QM;Somerman, MJ
通讯作者: Somerman, MJ
DOI: 10.1016/j.ymthe.2005.03.009
发表时间: 2005-08-01
期刊: MOLECULAR THERAPY
影响因子: 12.4
作者:
Zhao, ZR;Zhao, M;Franceschi, RT
通讯作者: Franceschi, RT
DOI: 10.1210/en.139.12.5125
发表时间: 1998-12-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
作者:
Boden, SD;Liu, YS;Titus, L
通讯作者: Titus, L