Bone morphogenetic protein 2 stimulates endochondral ossification by regulating periosteal cell fate during bone repair.
Bone morphogenetic protein 2 stimulates endochondral ossification by regulating periosteal cell fate during bone repair.
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DOI：
10.1016/j.bone.2010.03.012
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发表时间：
2010-07
期刊：
影响因子：
4.1
通讯作者：
Colnot, Celine
中科院分区：
文献类型：
--
作者：
Yu, Yan Yiu;Lieu, Shirley;Lu, Chuanyong;Colnot, Celine
关键词：
骨修复依赖于多种生长因子和细胞因子的协同作用来刺激新的骨组织形成。在所有涉及骨修复的生长因子中，骨形态发生蛋白（BMPs）是目前唯一用于治疗性促进愈合的分子。虽然bmp被认为是强骨诱导剂，但它们在启动骨骼修复中的作用尚未完全阐明。本研究的目的是确定BMP2在骨再生早期阶段的作用，更具体地说，是在调节骨骼祖细胞的命运。在非稳定骨折的软骨内成骨愈合过程中，外源性BMP2增加了软骨和骨的沉积和吸收，这与修复早期破骨细胞生成的刺激有关，但与血管生成无关。在稳定骨折的愈合过程中，通常通过膜内骨化发生，外源性BMP2诱导软骨形成，提示在调节细胞命运决定中起作用。具体来说，骨膜被发现是外源性BMP2的靶标，这是由该组织中BMP通路的激活所显示的。通过细胞谱系分析，我们进一步发现BMP2可以引导细胞向骨膜内的软骨细胞谱系分化，而不是向内膜分化，这表明骨膜和内膜内的骨骼祖细胞对BMP信号的反应不同。综上所述，BMP2在修复的早期阶段发挥了重要作用，通过在骨膜和内膜内募集骨骼祖细胞的局部来源，并决定它们向软骨和成骨谱系的分化。
Bone repair depends on the coordinated action of numerous growth factors and cytokines to stimulate new skeletal tissue formation. Among all the growth factors involved in bone repair, Bone Morphogenetic Proteins (BMPs) are the only molecules now used therapeutically to enhance healing. Although BMPs are known as strong bone inducers, their role in initiating skeletal repair is not entirely elucidated. The aim of this study was to define the role of BMP2 during the early stages of bone regeneration and more specifically in regulating the fate of skeletal progenitors. During healing of non-stabilized fractures via endochondral ossification, exogenous BMP2 increased the deposition and resorption of cartilage and bone, which was correlated with a stimulation of osteoclastogenesis but not angiogenesis in the early phase of repair. During healing of stabilized fractures, which normally occurs via intramembranous ossification, exogenous BMP2 induced cartilage formation suggesting a role in regulating cell fate decisions. Specifically, the periosteum was found to be a target of exogenous BMP2 as shown by activation of the BMP pathway in this tissue. Using cell lineage analyses, we further show that BMP2 can direct cell differentiation towards the chondrogenic lineage within the periosteum but not the endosteum, indicating that skeletal progenitors within periosteum and endosteum respond differently to BMP signals. In conclusion, BMP2 plays an important role in the early stages of repair by recruiting local sources of skeletal progenitors within periosteum and endosteum and by determining their differentiation towards the chondrogenic and osteogenic lineages.
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DOI：
10.1083/jcb.150.5.1085
发表时间：
2000-09-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lee JY;Qu-Petersen Z;Cao B;Kimura S;Jankowski R;Cummins J;Usas A;Gates C;Robbins P;Wernig A;Huard J
通讯作者：
Huard J
影响因子：
37.8
作者：
Farrington-Rock, C;Crofts, NJ;Canfield, AE
通讯作者：
Canfield, AE
影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
影响因子：
2.8
作者：
Luu, Hue H.;Song, Wen-Xin;He, Tong-Chuan
通讯作者：
He, Tong-Chuan
影响因子：
2.8
作者：
Lou, JR;Xu, F;Manske, P
通讯作者：
Manske, P