Sexual dimorphism in the effect of GDF-6 deficiency on murine tendon.

Sexual dimorphism in the effect of GDF-6 deficiency on murine tendon.
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DOI:
10.1002/jor.20916
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发表时间:
2009-12
影响因子:
2.8
通讯作者:
Bierwert, LouAnn
Bierwert, LouAnn
中科院分区:
医学3区
文献类型:
--
作者:
Mikic, Borjana;Rossmeier, Kerri;Bierwert, LouAnn

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骨形态发生蛋白中生长分化因子(GDF)亚家族的3个成员,GDF 5、6和7,具有增强肌腱和韧带修复的潜力。为了进一步了解这些分子在体内的作用,以前的研究描述了GDF5和GDF7功能性零突变小鼠的完整和愈合的肌腱。本研究的主要目标是详细描述4周龄和16周龄的GDF6-/-小鼠及其+/+小鼠的完整肌腱表型。结果表明,GDF6缺乏与肌腱表型改变有关,这种改变持续到成年。在男性中,GDF6/-尾腱束胶原蛋白和糖胺多糖含量显著减少,这些成分差异与材料性能受损有关。GDF6缺乏对肌腱的影响是性二态的,然而,在雌性GDF6-/-小鼠中,没有发现肌腱成分和材料特性的差异。在男性中观察到的肌腱表型在尾部似乎比在跟腱部位更强,那里存在一些成分差异,但没有发现材料特性的差异。这些数据支持现有的体外研究,这些研究表明BMP13(人类与GDF6的同源物)在肌腱基质建模和/或重塑中可能发挥作用。
Three members of the growth/differentiation factor (GDF) subfamily of bone morphogenetic proteins, GDFs 5, 6, and 7, have the potential to augment tendon and ligament repair. To gain further insight into the in vivo role of these molecules, previous studies characterized intact and healing tendons in mice with functional null mutations in GDFs 5 and 7. The primary goal of the present study was to perform a detailed characterization of the intact tendon phenotype in 4 and 16 week-old, male and female, GDF6 -/- mice and their +/+ littermates. The results demonstrate that GDF6 deficiency was associated with an altered tendon phenotype that persisted into adulthood. Among males, GDF6 -/- tail tendon fascicles had significantly less collagen and glycosaminoglycan content, and these compositional differences were associated with compromised material properties. The effect of GDF6 deficiency on tendon was sexually dimorphic, however, for among female GDF6 -/- mice, neither differences in tendon composition nor in material properties were detected. The tendon phenotype that was observed in males appeared to be stronger in the tail site than in the Achilles tendon site, where some compositional differences were present, but no material property differences were detected. These data support existing in vitro studies, which suggest a potential role for BMP13 (the human homologue to GDF6) in tendon matrix modeling and/or remodeling.
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