Identification of CITED2 as a negative regulator of fracture healing

被引：15

作者：

Lee, Jonathan Y. ^{[1
,2
]}

Taub, Peter J. ^{[2
]}

Wang, Liang ^{[3
]}

Clark, Amelia ^{[1
]}

Zhu, Ling L. ^{[1
,4
]}

Maharam, Edward R. ^{[1
]}

Leong, Daniel J. ^{[1
,5
]}

Ramcharan, Melissa ^{[1
,5
]}

Li, Zhengzhi ^{[1
]}

Liu, Zhonghou ^{[3
]}

Ma, Yuan-Zheng ^{[3
]}

Sun, Li ^{[4
]}

Zaidi, Mone ^{[4
]}

Majeska, Robert J. ^{[1
,5
]}

Sun, Hui B. ^{[1
]}

机构：

[1] Mt Sinai Sch Med, Leni & Peter W May Dept Orthopaed, New York, NY USA

[2] Mt Sinai Sch Med, Div Plast Surg, New York, NY USA

[3] Gen Hosp PLA, Clin Ctr 309, Dept Orthopaed, Beijing, Peoples R China

[4] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY USA

[5] CUNY City Coll, Dept Biomed Engn, New York, NY USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 387卷 / 04期

基金：

美国国家卫生研究院;

关键词：

CITED2; Bone fracture healing; ECM remodeling; Angiogenesis; Osteogenesis; Matrix metalloproteinases; ENDOCHONDRAL BONE-FORMATION; ENDOTHELIAL GROWTH-FACTOR; CREB-BINDING PROTEIN; MANDIBULAR FRACTURES; MICE LACKING; ANGIOGENESIS; CHONDROCYTES; GENE; ACTIVATION; EXPRESSION;

D O I：

10.1016/j.bbrc.2009.07.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The transcription regulator CITED2 (CBP/p300-Interacting-Transactivator-with-ED-rich-tail-2) is known to suppress genes mediating angiogenesis and extracellular matrix (ECM) remodeling. However, it is unclear whether CITED2 has a role in controlling skeletal repair or remodeling. We tested the hypothesis that CITED2 functions in bone fracture healing by suppressing the expression of genes critical to ECM remodeling, angiogenesis and osteogenesis, importantly the matrix metalloproteinases (MMPs). Three hours following mandibular osteotomy or sham surgery of adult rats, osteotomy fronts were harvested and the expression of CITED2 and genes associated with fracture healing was ascertained by quantitative PCR. In parallel, gain-of-function studies examined the effect of overexpressing CITED2 on the expression and activity of several MMPs. In the fractured mandible, CITED2 expression was inversely related to the expression of MMP-2,-3,-9,-13, VEGF, HIF-1 alpha, M-CSF, RANK-L, and OPG. Consistent with this, the overexpression of CITED2 in osteoblasts inhibited the expression and activity of MMP-2,-3,-9, and -13. Taken together, the studies suggest that CITED2 is a critical upstream regulator of fracture healing. The suppression of CITED2 early after fracture may allow an optimal initiation of the healing response. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：641 / 645

页数：5

共 35 条

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