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有读书笔记Differential effects between the loss of MMP-2 and MMP-9 on structural and tissue-level properties of bone

热1 dr.qinan 添加于 2011-1-5 08:50 | 3043 次阅读 | 3 个评论

  •  作 者

    Nyman JS, Lynch CC, Perrien DS, Thiolloy S, O'Quinn EC, Patil CA, Bi X, Pharr GM, Mahadevan-Jansen A, Mundy GR

  •  摘 要

    Matrix metalloproteinases (MMPs) are capable of processing certain components of bone tissue including type 1 collagen, a determinant of the biomechanical properties of bone tissue, and they are expressed by osteoclasts and osteoblasts. Therefore, we posit that MMP activity can affect the ability of bone to resist fracture. To explore this possibility, we determined the architectural, compositional, and biomechanical properties of bones from wild-type (WT), Mmp2(-/-), and Mmp9(-/-) female mice at 16 weeks of age. MMP-2 and MMP-9 have similar substrates, but are primarily expressed by osteoblasts and osteoclasts, respectively. Analysis of the trabecular compartment of the tibia metaphysis by micro-computed tomography (microCT) revealed that these MMPs influence trabecular architecture, not volume. Interestingly, the loss of MMP-9 improved the connectivity density of the trabeculae, whereas the loss of MMP-2 reduced this parameter. Similar differential effects in architecture were observed in the L5 vertebra, but bone volume fraction was lower for both Mmp2(-/-) and Mmp9(-/-) mice than for WT. The mineralization density and mineral-to-collagen ratio, as determined by microCT and Raman microspectroscopy, were lower in the Mmp2-/- bones compared to WT controls. Whole bone strength, as determined by three point bending or compression testing, and tissue-level modulus and hardness, as determined by nanoindentation, were less for Mmp2-/- than for WT bones. In contrast, the Mmp9-/- femurs were less tough with lower post-yield deflection (more brittle) than that of the WT femurs. Taken together, MMPs play a complex role in maintaining bone integrity with the cell type that expresses the MMP likely being a contributing factor to how the enzyme affects bone quality. (c) 2010 American Society for Bone and Mineral Research.

  •  详细资料

    • 文献种类: Journal Article
    • 期刊名称: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
    • 期刊缩写: J Bone Miner Res
    • 期卷页: 2010年
    • 地址: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN
    • ISBN: 0884-0431
    • 备注:PMID:21191960

  • 学科领域 生物医药 » 临床医学

  •  所属群组

    骨科学   医药科研动态   骨质疏松 (Osteoporos  

  • 相关链接 DOI URL 

  •  dr.qinan 的文献笔记  订阅

    MMPs基因敲除对骨结构和力学性能的影响
    根据文章的摘要，MMP2由成骨细胞表达，MMP9由破骨细胞表达。由于MMP在降解骨质方面，尤其是一型胶原方面有作用，因此，在敲除MMPs后，将可能会影响胶原的降解。作者比较MMP2和MMP9基因敲除后对骨结构，生化成分和力学性能的影响，得出结论为：
    1，MMPs基因敲除影响胫骨骨结构，而非骨量：
    MMP2基因敲除降低了胫骨骨小梁之间的连接，MMP9基因敲除增加了骨小梁之间的连接率；
    （还没看文献，我想这点是可预见的，MMP9参与破骨细胞骨吸收，缺少了MMP9后，骨小梁连接率自然应该增加；但是骨量没有增加，则反映了MMP9在骨吸收过程中起少量作用，真正起决定性作用的，还应该是cathepsin K之类的酶）
    然而，在腰椎L5,则MMPs基因敲除，不但影响了骨结构，而且使骨量均下降。（机制呢？这点比较有意思）
    2，MMPs基因敲除，导致骨的各个力学性能下降
    这点是可预见的
     
    上JBMR的理由呢？是因为比较了两个基因敲除小鼠么？
     
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发表评论 评论(3 人)

!reply! Dr.LinZhen 2011-1-5 09:22
文章使用了nanoindentation测量组织水平的生物力学性能， mark
!reply! dr.qinan 2011-1-5 09:44
对啊，这个是应该的。大体生物力学和微观力学。
!reply! Dr.LinZhen 2011-1-10 13:31
dr.qinan: 对啊，这个是应该的。大体生物力学和微观力学。
我想如果是从组织工程学材料开发的角度出发，微观力学的检测是重要的；但是从动物实验来讲，大体生物力学反映组织功能，微观力学可以反映什么呢？

facelist doodle 涂鸦板

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