Impaired remodeling phase of fracture repair in the absence of matrix metalloproteinase-2.
Impaired remodeling phase of fracture repair in the absence of matrix metalloproteinase-2.
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DOI：
10.1242/dmm.006304
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发表时间：
2011-03
影响因子：
4.3
通讯作者：
Colnot C
中科院分区：
文献类型：
--
作者：
Lieu S;Hansen E;Dedini R;Behonick D;Werb Z;Miclau T;Marcucio R;Colnot C
基质金属蛋白酶家族在骨骼的发育和修复中起着至关重要的作用，因为它们具有重塑细胞外基质和释放生物活性分子的能力。以前描述的大多数基质金属蛋白酶缺失的骨骼表型都是温和的，因此可以评估它们在成人骨修复过程中的功能。在人类和小鼠中，MMP2缺乏会导致肌肉骨骼表型。在这项研究中，我们评估了MMP2在小鼠骨折修复中的作用，并将其与MMP9和MMP13的作用进行了比较。MMP2在正常骨骼中低水平表达，在骨折骨痂中广泛表达。用普通的基质金属蛋白酶抑制剂GM6001治疗野生型小鼠，在骨折修复期间导致延迟的软骨重塑和骨形成，这类似于在Mmp9-/-小鼠中观察到的缺陷。与影响骨痂中软骨和骨的MMP9和MMP13缺失突变不同，MMP2缺失突变推迟了骨骼重建，但不会推迟软骨重建。与野生型相比，骨折骨痂的破骨细胞募集或血管侵袭均未发生改变，出现了这种改建缺陷。然而，通过原位杂交，我们没有检测到MMP2基因缺失小鼠的骨痂中MMP9、Mmp13或MT1-MMP14的表达变化，但我们观察到Timp2在MMP2、Mmp9和Mmp13基因缺失的小鼠骨痂中的表达降低。与MMP9和MMP13相比，MMP2与MMP2基因缺失小鼠的骨骼表型一致，在骨折骨痂中新生骨的重塑中发挥作用，并影响骨修复的后期阶段。综上所述，我们的结果表明，在骨折修复过程中，MMPs在调节骨骼组织沉积和重塑方面发挥着独特而独特的作用。
The matrix metalloproteinase (MMP) family of extracellular proteases performs crucial roles in development and repair of the skeleton owing to their ability to remodel the extracellular matrix (ECM) and release bioactive molecules. Most MMP-null skeletal phenotypes that have been previously described are mild, thus permitting the assessment of their functions during bone repair in the adult. In humans and mice, MMP2 deficiency causes a musculoskeletal phenotype. In this study, we assessed the role of MMP2 during mouse fracture repair and compared it with the roles of MMP9 and MMP13. Mmp2 was expressed at low levels in the normal skeleton and was broadly expressed in the fracture callus. Treatment of wild-type mice with a general MMP inhibitor, GM6001, caused delayed cartilage remodeling and bone formation during fracture repair, which resembles the defect observed in Mmp9–/– mice. Unlike Mmp9- and Mmp13-null mutations, which affect both cartilage and bone in the callus, the Mmp2-null mutation delayed bone remodeling but not cartilage remodeling. This remodeling defect occurred without changes in either osteoclast recruitment or vascular invasion of the fracture callus compared with wild type. However, we did not detect changes in expression of Mmp9, Mmp13 or Mt1-Mmp (Mmp14) in the calluses of Mmp2-null mice compared with wild type by in situ hybridization, but we observed decreased expression of Timp2 in the calluses of Mmp2-, Mmp9- and Mmp13-null mice. In keeping with the skeletal phenotype of Mmp2-null mice, MMP2 plays a role in the remodeling of new bone within the fracture callus and impacts later stages of bone repair compared with MMP9 and MMP13. Taken together, our results indicate that MMPs play unique and distinct roles in regulating skeletal tissue deposition and remodeling during fracture repair.
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DOI：
10.1083/jcb.200409115
发表时间：
2005-05-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lee S;Jilani SM;Nikolova GV;Carpizo D;Iruela-Arispe ML
通讯作者：
Iruela-Arispe ML
影响因子：
3.5
作者：
Kato, T;Kure, T;Azar, DT
通讯作者：
Azar, DT
影响因子：
4.6
作者：
Stickens, D;Behonick, DJ;Werb, Z
通讯作者：
Werb, Z
影响因子：
3.5
作者：
Mosig, Rebecca A.;Dowling, Oonagh;Martignetti, John A.
通讯作者：
Martignetti, John A.
影响因子：
4.8
作者：
Corry, DB;Kiss, A;Kheradmand, F
通讯作者：
Kheradmand, F