Chondrocyte BMP2 signaling plays an essential role in bone fracture healing

被引:105
作者
Mi, Meng [1 ,2 ]
Jin, Hongting [1 ,3 ]
Wang, Baoli [1 ,4 ]
Yukata, Kiminori [1 ]
Sheu, Tzong-jen [1 ]
Ke, Qiao Han
Tong, Peijian [3 ]
Im, Hee-Jeong
Xiao, Guozhi
Chen, Di [1 ,5 ]
机构
[1] Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14627 USA
[2] Jishuitan Hosp, Beijing, Peoples R China
[3] Zhejiang Chinese Med Univ, Inst Orthopaed & Traumatol, Hangzhou, Zhejiang, Peoples R China
[4] Tianjin Med Univ, Endocrine Res Inst, Tianjin, Peoples R China
[5] Rush Univ, Med Ctr, Dept Biochem, John W & Helen Watzek Endowed Chair, Chicago, IL 60612 USA
关键词
BMP2; Fracture healing; Fracture callus; Chondrocyte; Osteoblast; Conditional knockout; MESENCHYMAL STEM-CELLS; MEDIATED GENE-THERAPY; MORPHOGENETIC PROTEIN-2; SPINAL-FUSION; OSTEOGENIC DIFFERENTIATION; SEGMENTAL DEFECT; CRE RECOMBINASE; GROWTH-FACTOR; EXPRESSION; RATS;
D O I
10.1016/j.gene.2012.09.130
中图分类号
Q3 [遗传学];
学科分类号
071007 [遗传学];
摘要
The specific role of endogenous Bmp2 gene in chondrocytes and in osteoblasts in fracture healing was investigated by generation and analysis of chondrocyte- and osteoblast-specific Bmp2 conditional knockout (cKO) mice. The unilateral open transverse tibial fractures were created in these Bmp2 cKO mice. Bone fracture callus samples were collected and analyzed by X-ray, micro-CT, histology analyses, biomechanical testing and gene expression assays. The results demonstrated that the lack of Bmp2 expression in chondrocytes leads to a prolonged cartilage callus formation and a delayed osteogenesis initiation and progression into mineralization phase with lower biomechanical properties. In contrast, when the Bmp2 gene was deleted in osteoblasts, the mice showed no significant difference in the fracture healing process compared to control mice. These findings suggest that endogenous BMP2 expression in chondrocytes may play an essential role in cartilage callus maturation at an early stage of fracture healing. Our studies may provide important information for clinical application of BMP2. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:211 / 218
页数:8
相关论文
共 50 条
[1]
Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene [J].
Baltzer, AWA ;
Lattermann, C ;
Whalen, JD ;
Wooley, P ;
Weiss, K ;
Grimm, M ;
Ghivizzani, SC ;
Robbins, PD ;
Evans, CH .
GENE THERAPY, 2000, 7 (09) :734-739
[2]
Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model [J].
Bertone, AL ;
Pittman, DD ;
Bouxsein, ML ;
Li, J ;
Clancy, B ;
Seeherman, HJ .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2004, 22 (06) :1261-1270
[3]
BOLANDER ME, 1992, P SOC EXP BIOL MED, V200, P165
[4]
Biological mechanisms of bone and cartilage remodelling-genomic perspective [J].
Borovecki, F. ;
Pecina-Slaus, N. ;
Vukicevic, S. .
INTERNATIONAL ORTHOPAEDICS, 2007, 31 (06) :799-805
[5]
Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs) [J].
Cheng, HW ;
Jiang, W ;
Phillips, FM ;
Haydon, RC ;
Peng, Y ;
Zhou, L ;
Luu, HH ;
An, NL ;
Breyer, B ;
Vanichakarn, P ;
Szatkowski, JP ;
Park, JY ;
He, TC .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2003, 85A (08) :1544-1552
[6]
Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development [J].
Chung, UI ;
Schipani, E ;
McMahon, AP ;
Kronenberg, HM .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03) :295-304
[7]
COOK SD, 1994, CLIN ORTHOP RELAT R, P302
[8]
Mouse α1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast [J].
Dacquin, R ;
Starbuck, M ;
Schinke, T ;
Karsenty, G .
DEVELOPMENTAL DYNAMICS, 2002, 224 (02) :245-251
[9]
EINHORN TA, 1995, J BONE MINER RES, V10, P1272
[10]
Gazit D, 1999, J GENE MED, V1, P121, DOI 10.1002/(SICI)1521-2254(199903/04)1:2<121::AID-JGM26>3.0.CO