Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury.
Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury.
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DOI：
10.1371/journal.pone.0040602
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
O'Keefe RJ
中科院分区：
文献类型：
--
作者：
Loiselle AE;Frisch BJ;Wolenski M;Jacobson JA;Calvi LM;Schwarz EM;Awad HA;O'Keefe RJ
原发性肌腱修复后粘连的发病机制知之甚少，但被认为涉及基质金属蛋白酶（Mmps）的失调。我们以前已经证明，Mmp 9基因表达增加，在炎症阶段后，小鼠屈指肌腱（FDL）修复与粘连增加。为了进一步研究Mmp 9的作用，使用FDL肌腱修复模型在WT和Mmp 9 −/−小鼠中检查了愈合的细胞，分子和生物力学特征。WT中的粘连持续存在，但Mmp 9 −/−小鼠中的粘连减少了21天，强度没有任何降低。Mmp 9的缺失导致新肌腱相关基因Gdf 5和Smad 8的表达加速，I型胶原和III型胶原的表达延迟。此外，WT骨髓细胞（GFP+）特异性迁移至肌腱修复部位。将骨髓清除的Mmp 9 −/−小鼠与WT骨髓细胞移植导致比Mmp 9 −/−小鼠中观察到的更大的粘连，并且与WT小鼠中观察到的粘连相似。这些研究表明，Mmp 9主要来源于迁移到修复部位的骨髓细胞，并介导损伤肌腱中的粘连形成。Mmp 9是限制肌腱愈合中粘连形成的潜在靶点。
The pathogenesis of adhesions following primary tendon repair is poorly understood, but is thought to involve dysregulation of matrix metalloproteinases (Mmps). We have previously demonstrated that Mmp9 gene expression is increased during the inflammatory phase following murine flexor digitorum (FDL) tendon repair in association with increased adhesions. To further investigate the role of Mmp9, the cellular, molecular, and biomechanical features of healing were examined in WT and Mmp9−/− mice using the FDL tendon repair model. Adhesions persisted in WT, but were reduced in Mmp9−/− mice by 21 days without any decrease in strength. Deletion of Mmp9 resulted in accelerated expression of neo-tendon associated genes, Gdf5 and Smad8, and delayed expression of collagen I and collagen III. Furthermore, WT bone marrow cells (GFP+) migrated specifically to the tendon repair site. Transplanting myeloablated Mmp9−/− mice with WT marrow cells resulted in greater adhesions than observed in Mmp9−/− mice and similar to those seen in WT mice. These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured tendons. Mmp9 is a potential target to limit adhesion formation in tendon healing.
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影响因子：
15.9
作者：
Hoffmann, A;Pelled, G;Gazit, D
通讯作者：
Gazit, D
影响因子：
82.9
作者：
Bi, Yanming;Ehirchiou, Driss;Young, Marian F.
通讯作者：
Young, Marian F.
DOI：
10.1034/j.1600-0838.2000.010006312.x
发表时间：
2000-12-01
影响因子：
4.1
作者：
Kannus, P
通讯作者：
Kannus, P
影响因子：
15.9
作者：
Kollet, O;Shivtiel, S;Lapidot, T
通讯作者：
Lapidot, T
影响因子：
4.2
作者：
Karousou, Evgenia;Ronga, Mario;Maffulli, Nicola
通讯作者：
Maffulli, Nicola