Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital, Helsinki, Finland.
Clin Exp Rheumatol. 2010 Jul-Aug;28(4):511-8. Epub 2010 Aug 30.
Nucleosomal high mobility group box-1 (HMGB-1) is translocated and released from necrotic and activated cells as an endogenous danger signal (alarmin) and cytokine. It was hypothesised that it plays a role in osteoarthritis (OA). characterised by cellular activation, inflammation and enchondral bone formation.
Bovine knee joint samples, collected from culled animals, were scored using histologic/histochemical grading to intact looking, mild, moderate or severe and immunohistochemically stained for HMGB-1. Chondrocyte pellets, produced from human bone marrow-derived mesenchymal stem cells and stimulated with tumour necrosis factor-a (TNF-alpha), were similarly stained.
In healthy looking OA cartilage chondrocyte nuclei were usually HMGB-1 negative and in mild OA staining was restricted to nuclei. In moderate OA lesions HMGB-1 was also seen in the cytoplasm and occasionally pericellular matrix and in severe OA lesions often also in intra- and inter-territorial matrix. The tidemark in healthy cartilage did not contain HMGB-1, which however was seen at this interface as linear deposits even in intact-looking and mild OA lesions, as multiple wave-like deposits in moderate and as heavy granular deposits in severe lesions. TNF-alpha stimulation of chondrocytes caused translocation of HMGB-1 from the nucleus to the cytoplasm.
In resting chondrocytes tight nucleosomal HMGB-1 binding might cause steric hindrance of immunostaining. TNF-alpha- or OA-mediated activation leads to nuclear staining and cytoplasmic translocation. Advancing OA leads to increasingly intense extra-/pericellular deposition of HMGB-1 alarmin, indicating local chondrocyte activation and/or necrosis. In particular, HMGB-1 at the tidemark might play a role in the pathological thickening of subchondral bone plate/osteophyte formation.
核小体高迁移率族蛋白 B1（HMGB-1）作为一种内源性危险信号（警报素）和细胞因子，从坏死和活化的细胞中外渗和释放。据推测，它在骨关节炎（OA）中发挥作用。OA 的特征是细胞激活、炎症和软骨内骨形成。
从淘汰动物收集的牛膝关节样本，使用组织学/组织化学分级法进行评分，分为外观正常、轻度、中度或重度，并进行 HMGB-1 免疫组织化学染色。同样对人骨髓间充质干细胞来源的软骨细胞球进行刺激肿瘤坏死因子-α（TNF-α）后进行染色。
在外观正常的 OA 软骨中，软骨细胞核通常 HMGB-1 阴性，在轻度 OA 中染色仅限于核。在中度 OA 病变中，HMGB-1 也可见于细胞质中，偶尔见于细胞周围基质，在重度 OA 病变中，HMGB-1 也常见于细胞内和细胞间基质中。健康软骨的潮线不含 HMGB-1，但在外观正常和轻度 OA 病变中，可见线性沉积，在中度和重度病变中，可见呈波浪状的多个沉积和颗粒状的重沉积。TNF-α刺激软骨细胞导致 HMGB-1 从核转移到细胞质。
在静止的软骨细胞中，紧密核小体 HMGB-1 结合可能会阻碍免疫染色。TNF-α 或 OA 介导的激活导致核染色和细胞质易位。进展性 OA 导致 HMGB-1 在外周/细胞周围的沉积越来越多，表明局部软骨细胞激活和/或坏死。特别是，潮线处的 HMGB-1 可能在软骨下骨板/骨赘形成的病理性增厚中发挥作用。
