The role of transforming growth factor beta isoforms in tendon-to-bone healing

The role of transforming growth factor beta isoforms in tendon-to-bone healing
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DOI:
10.3109/03008207.2010.483026
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发表时间:
2011-04-01
影响因子:
2.9
通讯作者:
Thomopoulos, Stavros
Thomopoulos, Stavros
中科院分区:
医学3区
文献类型:
--
作者:
Kim, H. Mike;Galatz, Leesa M.;Thomopoulos, Stavros

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本研究的目的是检查三种转化生长因子β (TGF-β) 同工型中的两种在愈合肌腱至骨插入过程中的作用。 64 只大鼠的冈上肌腱在其骨附着处被横断并修复至肱骨头。每只大鼠的一侧肩膀接受渗透泵,用于在修复部位持续输送以下因子:(1)TGF-β1以及TGF-β2和3的中和抗体(TGF-β1组),(2)TGF-β3以及TGF-β1和2的中和抗体(TGF-β3组),(3)TGF-β1、2和3的中和抗体(抗TGF-β组),以及(4)生理盐水(生理盐水组)。对侧肩部接受盐水作为配对对照。使用基于组织学的测定和生物力学测试在死后的多个时间点对修复进行评估。与成对的对照肩部相比,接受 TGF-β1 治疗的肩部显示出 III 型胶原蛋白的产生增加,这表明存在疤痕介导的反应。 TGF-β1组有机械性能降低的趋势,但这些变化并未达到统计学显着性。与成对的对照肩部相比,抗TGF-β组的组织体积没有差异,但机械性能明显较差。与成对的对照肩部相比,TGF-β3 组没有表现出任何差异。尽管 TGF-β 同工型在肌腱至骨的发育和愈合中发挥重要作用,但使用渗透泵将外源 TGF-β 同工型和中和抗体应用于肩峰下间隙并不能改善冈上肌腱至骨的愈合。
The purpose of this study was to examine the role of two of the three transforming growth factor beta (TGF-beta) isoforms at the healing tendon-to-bone insertion. The supraspinatus tendons of 64 rats were transected at their bony insertions and repaired to the humeral head. One shoulder of each rat received an osmotic pump for sustained delivery of the following factors at the repair site: (1) TGF-beta 1 and neutralizing antibodies to TGF-beta 2 and 3 (TGF-beta 1 group), (2) TGF-beta 3 and neutralizing antibodies to TGF-beta 1 and 2 (TGF-beta 3 group), (3) neutralizing antibodies to TGF-beta 1, 2, and 3 (anti-TGF-beta group), and (4) saline (saline group). The contralateral shoulders received saline to serve as paired controls. The repairs were evaluated at multiple time points postmortem using histology-based assays and biomechanical testing. Treated shoulders in the TGF-beta 1 group showed increased type III collagen production compared to the paired control shoulders, indicative of a scar-mediated response. There was a trend toward reduced mechanical properties in the TGF-beta 1 group, but these changes did not reach statistical significance. The anti-TGF-beta group showed no difference in tissue volume, but significantly inferior mechanical properties, compared to the paired control shoulders. The TGF-beta 3 group did not show any differences compared to the paired control shoulders. Although TGF-beta isoforms play important roles in tendon-to-bone development and healing, application of exogenous TGF-beta isoforms and neutralizing antibodies to the subacromial space using osmotic pumps did not improve supraspinatus tendon-to-bone healing.