Differential Effects Between the Loss of MMP-2 and MMP-9 on Structural and Tissue-Level Properties of Bone
Differential Effects Between the Loss of MMP-2 and MMP-9 on Structural and Tissue-Level Properties of Bone
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DOI：
10.1002/jbmr.326
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发表时间：
2011-06-01
影响因子：
6.2
通讯作者：
Mundy, Gregory R.
中科院分区：
文献类型：
--
作者：
Nyman, Jeffry S.;Lynch, Conor C.;Mundy, Gregory R.
基质金属蛋白酶（MMP）能够加工骨组织的某些组分，包括1型胶原，其是骨组织的生物力学性质的决定因素，并且它们由破骨细胞和成骨细胞表达。因此，我们认为MMP活性可以影响骨抵抗骨折的能力。为了探索这种可能性，我们确定了16周龄野生型（WT）、Mmp 2（-/-）和Mmp 9（-/-）雌性小鼠骨骼的结构、组成和生物力学特性。MMP-2和MMP-9具有相似的底物，但分别主要由成骨细胞和破骨细胞表达。通过微计算机断层扫描（mu CT）分析胫骨干骺端的小梁室，发现这些MMPs影响小梁结构，而不是体积。有趣的是，MMP-9的缺失改善了小梁的连接密度，而MMP-2的缺失降低了该参数。在L-5椎骨中观察到类似的结构差异效应，但Mmp 2（-/-）和Mmp 9（-/-）小鼠的骨体积分数低于WT小鼠。通过mu CT和拉曼显微光谱测定，Mmp 2（-/-）骨中的矿化密度和矿物质与胶原蛋白的比例低于WT对照骨。通过三点弯曲或压缩测试测定的全骨强度以及通过纳米压痕测定的组织水平模量和硬度，Mmp 2（-/-）低于WT骨。相比之下，Mmp 9（-/-）股骨的坚韧较WT股骨低，且术后挠度较低（更脆）。总之，这些信息表明，MMP在维持骨完整性方面发挥着复杂的作用，表达MMP的细胞类型可能是酶如何影响骨质量的一个因素。(C)2011年美国骨与矿物质研究学会。
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 expressed primarily by osteoblasts and osteoclasts, respectively. Analysis of the trabecular compartment of the tibia metaphysis by micro-computed tomography (mu CT) 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 L-5 vertebra, but bone volume fraction was lower for both Mmp2(-/-) and Mmp9(-/-) mice than for WT mice. The mineralization density and mineral-to-collagen ratio, as determined by mu CT and Raman microspectroscopy, were lower in the Mmp2(-/-) bones than in WT control bones. 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 postyield deflection (more brittle) than the WT femurs. Taken together, this information reveals that 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) 2011 American Society for Bone and Mineral Research.