Englert Carsten, Blunk Torsten, Fierlbeck Johann, Kaiser Julia, Stosiek Wolfgang, Angele Peter, Hammer Joachim, Straub Rainer H
University Hospital Regensburg, Regensburg, Germany.
Arthritis Rheum. 2006 Dec;54(12):3890-7. doi: 10.1002/art.22250.
Posttraumatic integration of articular cartilage at fracture sites is essential for mechanical stability of cartilage, and ruptured cartilage is a prerequisite for early osteoarthritis. This study was undertaken to investigate effects on articular cartilage integration mediated by steroid hormones, interleukin-1beta (IL-1beta), and combinations thereof.
Articular cartilage blocks were cultured in partial apposition for 2 weeks with ascorbic acid, testosterone, 17beta-estradiol, and dehydroepiandrosterone (DHEA), with or without IL-1beta. Mechanical integration was measured as adhesive strength, i.e., the maximum force at rupture of integrated cartilage blocks divided by the overlap area. Glycosaminoglycan content was used to study synthesized extracellular matrix.
Culture in medium without supplements did not lead to integration (adhesive strength 0 kPa). With administration of ascorbic acid (100 microg/ml), the median adhesive strength was 49 kPa. In comparison with ascorbic acid alone, all steroid hormones induced a strong, concentration-dependent stimulation of integration (with maximum values observed with DHEA at 3 x 10(-5)M, testosterone at 10(-8)M, and 17beta-estradiol at 10(-11)M). For testosterone and 17beta-estradiol, this was also reflected by an increase of glycosaminoglycan content. Adhesive strength was increased with IL-1beta at 10 pg/ml, but not at 1 pg/ml or 100 pg/ml. In the presence of both IL-1beta and sex hormones, integration of articular cartilage was reduced.
This is the first study to demonstrate that steroid hormones such as 17beta-estradiol, DHEA, and testosterone stimulate articular cartilage integration. This effect is abrogated by low concentrations of IL-1beta. In the absence of IL-1beta or after neutralization of IL-1beta, steroid hormones might be favorable adjuvant compounds to optimize cartilage integration.
创伤后关节软骨在骨折部位的整合对于软骨的机械稳定性至关重要,而软骨破裂是早期骨关节炎的一个先决条件。本研究旨在探讨类固醇激素、白细胞介素-1β(IL-1β)及其组合对关节软骨整合的影响。
将关节软骨块在部分贴合状态下培养2周,添加或不添加IL-1β,并添加抗坏血酸、睾酮、17β-雌二醇和脱氢表雄酮(DHEA)。机械整合通过黏附强度来衡量,即整合后的软骨块破裂时的最大力除以重叠面积。糖胺聚糖含量用于研究合成的细胞外基质。
在无补充剂的培养基中培养不会导致整合(黏附强度为0 kPa)。添加抗坏血酸(100μg/ml)后,中位黏附强度为49 kPa。与单独使用抗坏血酸相比,所有类固醇激素均诱导出强烈的、浓度依赖性的整合刺激(DHEA在3×10⁻⁵M、睾酮在10⁻⁸M、17β-雌二醇在10⁻¹¹M时观察到最大值)。对于睾酮和17β-雌二醇,这也表现为糖胺聚糖含量的增加。IL-1β在10 pg/ml时黏附强度增加,但在1 pg/ml或100 pg/ml时未增加。在同时存在IL-1β和性激素的情况下,关节软骨的整合减少。
这是第一项证明17β-雌二醇、DHEA和睾酮等类固醇激素刺激关节软骨整合的研究。低浓度的IL-1β可消除这种作用。在不存在IL-1β或IL-1β被中和后,类固醇激素可能是优化软骨整合的有利辅助化合物。