The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing.
The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing.
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DOI：
10.1016/j.matbio.2016.02.007
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Luan X
中科院分区：
文献类型：
--
作者：
Lu X;Li W;Fukumoto S;Yamada Y;Evans CA;Diekwisch T;Luan X
细胞外基质（ECM）在骨折愈合的所有阶段提供结构支持、细胞迁移锚定、细胞分化线索和微调细胞增殖信号，包括软骨愈伤组织形成、愈伤组织重塑和骨折间隙的骨桥。在本研究中，我们确定了细胞外基质蛋白成釉细胞素（AMBN）在小鼠长骨骨折抵抗和骨折愈合中的作用。为此，我们对WT和AMBNΔ5-6截断模型小鼠的长骨进行了生物力学分析、骨折愈合试验和干细胞集落形成比较。还确定了外源AMBN对断裂部位的影响。我们的数据表明，骨基质中缺乏功能性AMBN导致股骨骨量减少31%，能量减少40%。在细胞水平上，AMBN功能抑制降低了骨折修复愈伤组织细胞的增殖能力，PCNA减少58%，Cyclin D1基因表达减少40%，以及PCNA免疫组化。在骨折愈合方面，AMBN截断与软骨形成期增强和延长相关，导致矿化组织基因表达延迟，骨折修复骨痂的骨化延迟。骨折后一周，AMBN在骨折部位的表达增加了6.9倍，并且在骨折间隙有明显的AMBN免疫标记，这突显了AMBN在骨折愈合中的作用。最后，将外源性AMBN蛋白应用于骨折部位加速了骨痂形成和骨折愈合（骨量增加33%，骨矿物质密度增加19%），验证了我们的AMBN功能丧失研究结果。总之，这些数据证明了AMBN细胞外基质蛋白在骨折预防和骨折快速愈合中的功能重要性。
The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBNΔ5-6 truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing.
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影响因子：
2.4
作者：
Kallai, Ilan;van Lenthe, G. Harry;Ruffoni, Davide;Zilberman, Yoram;Muller, Ralph;Pelled, Gadi;Gazit, Dan
通讯作者：
Gazit, Dan
影响因子：
4.1
作者：
Lu, Xuanyu;Ito, Yoshihiro;Atsawasuwan, Phimon;Dangaria, Smit;Yan, Xiulin;Wu, Tuojiang;Evans, Carla A.;Luan, Xianghong
通讯作者：
Luan, Xianghong
影响因子：
168.9
作者：
Kanis, JA
通讯作者：
Kanis, JA
DOI：
10.2106/00004623-197557070-00013
发表时间：
1975-01-01
影响因子：
5.3
作者：
BURSTEIN, AH;ZIKA, JM;KLEIN, L
通讯作者：
KLEIN, L
影响因子：
7.6
作者：
Chun, Y. -H. P.;Lu, Y.;Simmer, J. P.
通讯作者：
Simmer, J. P.