Collagen V haploinsufficiency in a murine model of classic Ehlers-Danlos syndrome is associated with deficient structural and mechanical healing in tendons.
Collagen V haploinsufficiency in a murine model of classic Ehlers-Danlos syndrome is associated with deficient structural and mechanical healing in tendons.
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DOI：
10.1002/jor.23571
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Soslowsky LJ
中科院分区：
文献类型：
--
作者：
Johnston JM;Connizzo BK;Shetye SS;Robinson KA;Huegel J;Rodriguez AB;Sun M;Adams SM;Birk DE;Soslowsky LJ
由于COL5a1或COL5a2基因的杂合突变，经典的Ehler-Danlos综合征(EDS)患者患有结缔组织超弹性、关节不稳定、皮肤超伸性、组织脆性和创面愈合不良。本研究利用COL5a1+/−小鼠研究了V型胶原在未损伤的髌腱中建立结构和功能的作用以及在损伤反应中的作用。这些分析是通过比较经典的EDS模型(Col5a1+/−)和野生型对照的肌腱完成的。分别于伤前、伤后3周和6周对肌腱进行力学测试、组织学和纤维分析。我们发现，与正常的野生型肌腱相比，COL5a1+/−肌腱损伤后的力学能力恢复较慢，而正常的野生型肌腱在损伤后6周恢复到损伤前的水平。此外，与野生型肌腱相比，COL5a1+/−肌腱的纤维形态和直径分布发生了变化。本研究表明，V型胶原在肌腱损伤后胶原纤维的形成及相关的力学完整性的恢复中起重要作用。此外，EDS中V型胶原表达减少的失调与损伤反应减弱有关。本文提出的结果有可能指导未来针对经典EDS患者的靶向治疗。
Classic Ehlers-Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. This study investigated the roles of collagen V in establishing structure and function in uninjured patellar tendons as well as in the injury response using a Col5a1+/− mouse, a model for classic EDS. These analyses were done comparing tendons from a classic EDS model (Col5a1+/−) with wild type controls. Tendons were subjected to mechanical testing, histological and fibril analysis before injury as well as 3 weeks and 6 weeks after injury. We found that Col5a1+/− tendons demonstrated diminished recovery of mechanical competency after injury as compared to normal wild type tendons, which recovered their pre-injury values by 6 weeks post injury. Additionally, the Col5a1+/−tendons demonstrated altered fibril morphology and diameter distributions compared to the wild type tendons. This study indicates that collagen V plays an important role in regulating collagen fibrillogenesis and the associated recovery of mechanical integrity in tendons after injury. In addition, the dysregulation with decreased collagen V expression in EDS is associated with a diminished injury response. The results presented herein have the potential to direct future targeted therapeutics for classic EDS patients.
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影响因子：
3.8
作者：
Dunkman, Andrew A.;Buckley, Mark R.;Mienaltowski, Michael J.;Adams, Sheila M.;Thomas, Stephen J.;Satchell, Lauren;Kumar, Akash;Pathmanathan, Lydia;Beason, David P.;Iozzo, Renato V.;Birk, David E.;Soslowsky, Louis J.
通讯作者：
Soslowsky, Louis J.
影响因子：
1.9
作者：
GELBERMAN, RH;VANDEBERG, JS;AKESON, WH
通讯作者：
AKESON, WH
影响因子：
2.4
作者：
Beason, David P.;Kuntz, Andrew F.;Soslowsky, Louis J.
通讯作者：
Soslowsky, Louis J.
DOI：
10.1115/1.4023234
发表时间：
2013-02-01
影响因子：
1.7
作者：
Connizzo, Brianne K.;Sarver, Joseph J.;Soslowsky, Louis J.
通讯作者：
Soslowsky, Louis J.
DOI：
10.1097/00005768-199703000-00005
发表时间：
1997-03-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Davidson, CJ;Ganion, LR;Sevier, TL
通讯作者：
Sevier, TL