Altered Skeletal Expression of Sclerostin and Its Link to Radiographic Progression in Ankylosing Spondylitis
Altered Skeletal Expression of Sclerostin and Its Link to Radiographic Progression in Ankylosing Spondylitis
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DOI：
10.1002/art.24888
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发表时间：
2009-11-01
影响因子：
--
通讯作者：
Schett, Georg
中科院分区：
文献类型：
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作者：
Appel, Heiner;Ruiz-Heiland, Gisela;Schett, Georg
客观的。骨细胞通过特异性表达硬化素（一种骨形成抑制剂）被认为是骨损伤的传感器和骨量的调节剂。骨细胞在调节关节炎局部骨重塑中的作用尚不清楚。本研究的目的是探讨骨细胞在强直性脊柱炎 (AS) 骨重塑中的作用。方法。通过免疫组织化学方法评估来自 AS 患者、类风湿性关节炎 (RA) 患者、骨关节炎 (OA) 患者以及对照受试者的关节中的硬化蛋白表达和骨细胞死亡。此外，通过酶联免疫吸附测定法评估了健康受试者和 AS 患者的血清硬化素水平；该评估包括血清硬化素水平与 AS 患者脊柱放射学进展的纵向相关性。结果。硬化蛋白表达仅局限于骨细胞。虽然健康个体和 RA 患者的大多数骨细胞呈硬化蛋白阳性，但 OA 患者的表达显着降低，而 AS 患者的表达几乎不存在。此外，AS 患者的血清硬化素水平显着低于健康个体。重要的是，AS 患者血清硬化素水平较低与新韧带骨赘的形成显着相关 (P = 0.007)。结论。 AS 患者的硬化蛋白表达受损，表明该疾病中骨细胞功能发生了特定改变。 AS 患者血清中低水平的硬化素与结构损伤增加有关，这强调了硬化素在抑制骨形成中的作用。
Objective. Osteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS).Methods. Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS.Results. Sclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P = 0.007).Conclusion. Sclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.