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雌激素可减少成熟关节软骨中与机械损伤相关的细胞死亡和蛋白聚糖降解,与浅层组织的存在无关。

Estrogen reduces mechanical injury-related cell death and proteoglycan degradation in mature articular cartilage independent of the presence of the superficial zone tissue.

机构信息

Anatomisches Institut, Christian-Albrechts-Universität Kiel, Germany.

出版信息

Osteoarthritis Cartilage. 2013 Nov;21(11):1738-45. doi: 10.1016/j.joca.2013.07.007. Epub 2013 Jul 14.

Abstract

OBJECTIVE

To study the effect of 17β-estradiol (E2) and the superficial zone (SFZ) on cell death and proteoglycan degradation in articular cartilage after a single injurious compression in vitro.

METHOD

Cartilage explants from the femoropatellar groove of 2 year old cows with or without the SFZ were cultured serum-free with physiological concentrations of E2 and injured by an unconfined single load compression (strain 50%, velocity 2 mm/s). After 96 h cell death was measured histomorphometrically (nuclear blebbing (NB) and TUNEL staining) and release of glycosaminoglycans (GAG) by DMMB assay.

RESULTS

Injurious compression increased significantly the number of cells with NB and TUNEL staining and release of GAG. Physiological concentrations of E2 prevented the injury-related cell death and reduced the GAG release significantly in a receptor-mediated manner (shown by co-stimulation with the antiestrogen fulvestrant/faslodex/ICI-182,780). The presence of the SFZ did not alter the NB response to either the mechanical injury or E2, but reduced the overall release of GAG significantly.

CONCLUSION

E2 prevents injury-related cell death and GAG release, and might be useful for the development of treatment options for either cartilage-related sports injuries or osteoarthritis (OA). The SFZ does not seem to play an important role in (1) the E2-related tissue response and (2) the mechanically-induced cell death in deeper regions of the explants and GAG release. The latter might be related to the unconfined nature of the injury model.

摘要

目的

研究 17β-雌二醇(E2)和表层区(SFZ)对体外单次损伤性压缩后关节软骨细胞死亡和蛋白聚糖降解的影响。

方法

从 2 岁奶牛的髌股沟取出软骨外植体,有无 SFZ,在无血清条件下用生理浓度的 E2 培养,并通过无约束的单次负荷压缩(应变 50%,速度 2mm/s)进行损伤。96 小时后,通过核泡(NB)和 TUNEL 染色的组织形态计量学测量细胞死亡,并通过 DMMB 测定法测量糖胺聚糖(GAG)的释放。

结果

损伤性压缩显著增加了具有 NB 和 TUNEL 染色以及 GAG 释放的细胞数量。生理浓度的 E2 以受体介导的方式防止了与损伤相关的细胞死亡,并显著减少了 GAG 的释放(通过与抗雌激素氟维司群/ Faslodex/ICI-182780 共同刺激显示)。SFZ 的存在并没有改变机械损伤或 E2 对 NB 的反应,但显著减少了 GAG 的整体释放。

结论

E2 可防止与损伤相关的细胞死亡和 GAG 释放,可能有助于开发治疗与软骨相关的运动损伤或骨关节炎(OA)的治疗选择。SFZ 似乎在(1)E2 相关组织反应和(2)外植体深层区域的机械诱导细胞死亡和 GAG 释放方面没有发挥重要作用。后者可能与损伤模型的无约束性质有关。

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