BMP2 induces segment-specific skeletal regeneration from digit and limb amputations by establishing a new endochondral ossification center.
BMP2 induces segment-specific skeletal regeneration from digit and limb amputations by establishing a new endochondral ossification center.
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DOI：
10.1016/j.ydbio.2012.09.021
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发表时间：
2012-12-15
影响因子：
2.7
通讯作者：
Muneoka K
中科院分区：
文献类型：
--
作者：
Yu L;Han M;Yan M;Lee J;Muneoka K
骨形态发生蛋白（BMP）是骨发育、受损骨骼组织修复和小鼠趾尖再生所必需的。以前我们表明，BMP治疗可以诱导再生反应，在小鼠手指截肢在近端水平的终端指骨元素（P3）。在这项研究中，我们发现BMP 2的再生诱导能力延伸到新生儿手指的第二指骨元件（P2）和成人肢体的后肢的截肢。在这些模型中，诱导的再生反应以节段特异性方式受到限制，因此截肢的骨骼元件再生远端图案化的骨骼结构，但不形成关节或更远端的骨骼元件。对P2截肢的研究表明，BMP 2诱导的再生与局部增殖反应和已建立的指胚标记基因的瞬时表达有关。随后在骨残端远端形成新的软骨内骨化中心。软骨内骨化中心包含增殖的软骨细胞，其建立远端增殖区并向近端分化成肥大的软骨细胞。骨再生从近端到远端发生，成骨细胞的出现与截肢残端连续分化。使用的极性的endochondrialossification中心诱导的BMP 2在两个不同的截肢水平，我们表明，BMP 2激活水平依赖性再生反应指示的位置信息网络。总之，我们的研究提供的证据表明，BMP 2通过刺激一个新的软骨内骨化中心，利用现有的位置信息网络来调节骨骼再生过程中的模式，诱导哺乳动物肢体结构的再生。
Bone morphogenetic proteins (BMPs) are required for bone development, the repair of damage skeletal tissue, and the regeneration of the mouse digit tip. Previously we showed that BMP treatment can induce a regeneration response in mouse digits amputated at a proximal level of the terminal phalangeal element (P3). In this study, we show that the regeneration-inductive ability of BMP2 extends to amputations at the level of the second phalangeal element (P2) of neonatal digits, and the hindlimb of adult limbs. In these models the induced regenerative response is restricted in a segment-specific manner, thus amputated skeletal elements regenerate distally patterned skeletal structures but does not form joints or more distal skeletal elements. Studies on P2 amputations indicate that BMP2-induced regeneration is associated with a localized proliferative response and the transient expression of established digit blastema marker genes. This is followed by the formation of a new endochondral ossification center at the distal end of the bone stump. The endochondral ossification center contains proliferating chondrocytes that establish a distal proliferative zone and differentiate proximally into hypertrophic chondrocytes. Skeletal regeneration occurs from proximal to distal with the appearance of osteoblasts that differentiate in continuity with the amputated stump. Using the polarity of the endochondral ossification centers induced by BMP2 at two different amputation levels, we show that BMP2 activates a level-dependent regenerative response indicative of a positional information network. In summary, our studies provide evidence that BMP2 induces the regeneration of mammalian limb structures by stimulating a new endochondral ossification center that utilizes an existing network of positional information to regulate patterning during skeletal regeneration.
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影响因子：
2.1
作者：
Muneoka, Ken;Allan, Christopher H.;Han, Manjong
通讯作者：
Han, Manjong
影响因子：
56.9
作者：
FRENCH, V;BRYANT, PJ;BRYANT, SV
通讯作者：
BRYANT, SV
DOI：
10.1073/pnas.0905851106
发表时间：
2010-02-23
影响因子：
11.1
作者：
Agrawal, Vineet;Johnson, Scott A.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
2.7
作者：
Endo, T;Bryant, SV;Gardiner, DM
通讯作者：
Gardiner, DM
影响因子：
2.5
作者：
Masaki, Hideki;Ide, Hiroyuki
通讯作者：
Ide, Hiroyuki