Department of Clinical Laboratory, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264100, PR China.
Center of Translational Medicine, Zibo Central Hospital Affiliated to Shandong University, 54 Gongqingtuan Xi Road, Zibo 255036, PR China.
Life Sci. 2019 Jan 1;216:227-232. doi: 10.1016/j.lfs.2018.11.054. Epub 2018 Nov 27.
The tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) participates in multiple inflammatory diseases. However, its underlying mechanism in osteoporosis has not been elucidated. The aim of current study is to preliminarily clarify the function of TIPE2 in the pathogenesis of osteoporosis.
TIPE2 expression in patients with osteoporosis was measured by Western blot and qRT-PCR methods. Proinflammatory cytokines including TNF-α, IL-1 and IL-6 were assessed via enzyme-linked immunosorbent assay. Serum fasting PINP and β-CTX were measured by the chemiluminescence method. Simple logistic regression analysis was performed for the odds ratio (OR) for TIPE2.
TIPE2 expression in patients with osteoporosis was dramatically decreased and negatively correlated with proinflammatory cytokines. Furthermore, TIPE2 level was negatively correlated with fasting β-CTX, but not PINP, indicating that TIPE2 participates in the pathogenesis of osteoporosis dominantly by supression of bone resorption. Interestingly, TIPE2 expression level was positively correlated with bone mineral density (BMD), and its expression level can predict the risk of bone fracture using the simple logistic regression assay.
Our findings clarify that TIPE2 alleviates the pathogenesis of osteoporosis by suppressing the inflammatory status and the ability of TIPE2 for predicts bone fracture further demonstrated that TIPE2 might serve as a novel diagnostic marker and a therapeutic target for osteoporosis.
肿瘤坏死因子(TNF)-α诱导蛋白 8 样 2(TIPE2)参与多种炎症性疾病。然而,其在骨质疏松症中的潜在机制尚未阐明。本研究旨在初步阐明 TIPE2 在骨质疏松症发病机制中的作用。
通过 Western blot 和 qRT-PCR 方法测定骨质疏松症患者 TIPE2 的表达。通过酶联免疫吸附试验测定 TNF-α、IL-1 和 IL-6 等促炎细胞因子。用化学发光法测定血清空腹 PINP 和 β-CTX。采用简单逻辑回归分析 TIPE2 的比值比(OR)。
骨质疏松症患者 TIPE2 的表达显著降低,与促炎细胞因子呈负相关。此外,TIPE2 水平与空腹 β-CTX 呈负相关,而与 PINP 无关,表明 TIPE2 主要通过抑制骨吸收参与骨质疏松症的发病机制。有趣的是,TIPE2 的表达水平与骨密度(BMD)呈正相关,其表达水平可通过简单逻辑回归分析预测骨折风险。
我们的研究结果阐明了 TIPE2 通过抑制炎症状态和 TIPE2 抑制骨吸收的能力来减轻骨质疏松症的发病机制,进一步证明了 TIPE2 可能作为骨质疏松症的新型诊断标志物和治疗靶点。