Department of Nephrology, the Affiliated Geriatric Hospital of Nanjing Medical University, Nanjing 210024, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Aug 25;54(8):1080-1089. doi: 10.3724/abbs.2022094.
Diabetes osteoporosis is a chronic complication of diabetes mellitus (DM) and is associated with osteoclast formation and enhanced bone resorption. Specnuezhenide (SPN) is an active compound with anti-inflammatory and immunomodulatory properties. However, the roles of SPN in diabetic osteoporosis remain unknown. In this study, primary bone marrow macrophages (BMMs) were pretreated with SPN and were stimulated with receptor activator of nuclear factor kappa B ligand (RANKL; 50 ng/mL) to induce osteoclastogenesis. The number of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. The protein levels of cellular oncogene fos/nuclear factor of activated T cells c1 (c-Fos/NFATc1), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinases (MAPKs) were evaluated by western blot analysis. NF-κB luciferase assays were used to examine the role of SPN in NF-κB activation. The DM model group received a high-glucose, high-fat diet and was then intraperitoneally injected with streptozotocin (STZ). Micro-CT scanning, serum biochemical analysis, histological analysis were used to assess bone loss. We found that SPN suppressed RANKL-induced osteoclast formation and that SPN inhibited the expression of osteoclast-related genes and / . SPN inhibited RANKL-induced activation of NF-κB and MAPKs. experiments revealed that SPN suppressed diabetes-induced bone loss and the number of osteoclasts. Furthermore, SPN decreased the levels of bone turnover markers and increased the levels of runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), calcium (Ca) and phosphorus (P). SPN also regulated diabetes-related markers. This study suggests that SPN suppresses diabetes-induced bone loss by inhibiting RANKL-induced osteoclastogenesis, and provides an experimental basis for the treatment of diabetic osteoporosis.
糖尿病性骨质疏松症是糖尿病（DM）的一种慢性并发症，与破骨细胞形成和增强的骨吸收有关。獐牙菜苦苷（SPN）是一种具有抗炎和免疫调节作用的活性化合物。然而，SPN 在糖尿病性骨质疏松症中的作用尚不清楚。在这项研究中，用 SPN 预处理原代骨髓巨噬细胞（BMM），并用核因子κB 受体激活剂配体（RANKL；50ng/ml）刺激诱导破骨细胞形成。通过抗酒石酸酸性磷酸酶（TRAP）染色检测破骨细胞数量。通过 Western blot 分析评估细胞癌基因 fos/激活 T 细胞核因子 c1（c-Fos/NFATc1）、核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPKs）的蛋白水平。NF-κB 荧光素酶测定用于研究 SPN 在 NF-κB 激活中的作用。DM 模型组接受高糖、高脂饮食，然后腹腔注射链脲佐菌素（STZ）。采用 micro-CT 扫描、血清生化分析、组织学分析评估骨丢失。我们发现 SPN 抑制了 RANKL 诱导的破骨细胞形成，并且 SPN 抑制了破骨细胞相关基因的表达。SPN 抑制了 RANKL 诱导的 NF-κB 和 MAPKs 的激活。进一步的实验表明，SPN 抑制了糖尿病引起的骨丢失和破骨细胞数量的增加。此外，SPN 降低了骨转换标志物的水平，增加了 runt 相关转录因子 2（RUNX2）、骨保护素（OPG）、钙（Ca）和磷（P）的水平。SPN 还调节了与糖尿病相关的标志物。本研究表明，SPN 通过抑制 RANKL 诱导的破骨细胞形成来抑制糖尿病引起的骨丢失，为治疗糖尿病性骨质疏松症提供了实验依据。
