Expression of osteonectin and matrix Gla protein in scleroderma patients with and without calcinosis

Expression of osteonectin and matrix Gla protein in scleroderma patients with and without calcinosis
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DOI:
10.1093/rheumatology/kei277
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发表时间:
2006-11-01
期刊:
影响因子:
5.5
通讯作者:
Herrick, A. L.
Herrick, A. L.
中科院分区:
医学1区
文献类型:
--
作者:
Davies, C. A.;Jeziorska, M.;Herrick, A. L.

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目标.我们的目的是评估(i)骨基质蛋白骨连接素和基质γ-羧基谷氨酸蛋白(MGP)是否在系统性硬化症(SSc)患者的皮肤活检中上调;(ii)是否有皮肤钙质沉着症(SSc的一种令人痛苦和衰弱的并发症)患者之间的差异表达。从38名患有局限性皮肤SSc亚型的SSc患者[17名无钙质沉着症(lcSSc)和21名有钙质沉着症(lcSScCal)]和11名健康对照受试者的前臂采集皮肤穿刺活检。免疫组织化学进行抗体骨粘连蛋白和MGP。染色半定量评估微血管内皮细胞和真皮成纤维细胞。采用Kruskal-Wallis单因素方差分析比较患者组间的数据。与对照组相比,lcSSc和lcSScCal组具有骨连接素阳性内皮细胞(EC)的微血管百分比(尤其是lcSScCal组)均显示出统计学显著性增加,而单独lcSScCal组具有MGP阳性EC的微血管百分比增加。在两个SSc组中,网状真皮中骨粘连蛋白和MGP染色的成纤维细胞的百分比增加(对于骨粘连蛋白,这在lcSScCal组中更明显)。在乳头状真皮中,两个SSc组中骨连接素染色的成纤维细胞的百分比增加,但单独的lcSScCal组中MGP染色的成纤维细胞的百分比更高。与对照组相比,SSc患者的骨连接素和MGP蛋白表达普遍较高,lcSScCal患者的EC和成纤维细胞中骨连接素的表达显著高于无钙质沉着的lcSSc患者。
Objectives. Our aim was to evaluate (i) whether the bone matrix proteins osteonectin and matrix gamma-carboxyglutamic acid protein (MGP) are up-regulated in skin biopsies from patients with systemic sclerosis (SSc) and (ii) whether there is differential expression between patients with and without dermal calcinosis, a distressing and debilitating complication of SSc.Methods. Skin punch biopsies were taken from the forearms of 38 SSc patients with the limited cutaneous subtype of SSc [17 without calcinosis (lcSSc) and 21 with calcinosis (lcSScCal)] and from 11 healthy control subjects. Immunohistochemistry was performed with antibodies to osteonectin and MGP. Staining was assessed semiquantitatively in the microvascular endothelium and in dermal fibroblasts. The Kruskal-Wallis one-way ANOVA was used to compare the data between patient groups.Results. Both lcSSc and lcSScCal groups showed a statistically significant increase in the percentage of microvessels with osteonectin-positive endothelial cells (EC) (especially the lcSScCal group), whereas lcSScCal alone showed an increase in the percentage of microvessels with MGP-positive EC when compared with controls. In both SSc groups, the percentage of osteonectin and MGP-stained fibroblasts was increased in the reticular dermis (for osteonectin this was more marked in the lcSScCal group). In the papillary dermis, the percentage of osteonectin-stained fibroblasts was increased in both SSc groups but the lcSScCal group alone had a higher percentage of MGP-stained fibroblasts.Conclusions. When compared with controls, protein expression of osteonectin and MGP was greater in SSc patients generally, and osteonectin expression was significantly higher in EC and fibroblasts of the lcSScCal patients than the lcSSc patients without calcinosis.