Department of Pharmacology, Medical Division, National Research Centre, Giza, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Fundam Clin Pharmacol. 2022 Oct;36(5):869-878. doi: 10.1111/fcp.12779. Epub 2022 Apr 19.
Great attention was recently given to the importance of RAS in controlling inflammatory bone diseases, following the discovery of its local existence in skeletal tissues. Local RAS was found to be expressed on osteoblastic and osteoclastic cells and to exert its action via angiotensin II (AngII) receptors, including angiotensin II type 1 receptor (AT R) and angiotensin II type 2 receptors. Telmisartan (TLM), an AT R blocker (ARBs), was investigated in the present study for its therapeutic effect on bone health in osteoporotic rats. d-Galactose, a reducing sugar at a dose of 200 mg/kg/day/i.p., was used to induce osteoporosis in male rats. TLM, at a dose of 5 mg/kg/day, was orally introduced in the osteoporotic rats for four consecutive weeks. Tibia and femur bone densitometry was estimated, bone formation and bone resorption biomarkers serum levels were measured, mineral content in blood was also valued, and finally the extracellular regulated kinase (ERK) expression in bone was determined. TLM considerably improved the deleterious effect of d-galactose on bone mineral density. It blunted serum bone-specific alkaline phosphatase and osteocalcin while elevating serum osteoprotegrin (OPG). On the other hand, TLM turned off the pronounced elevation in serum receptor activator of nuclear factor-κβ ligand (RANKL), tartrate-resistant acid phosphatase, and cathepsin K. Furthermore, it significantly hindered the bone expression of ERK which hampered osteoclastogenesis. AT R inhibition abolished the rise in serum calcium and phosphorus and normalized serum superoxide dismutase and catalase. These TLM protective effects in d-galactose-treated rats were confirmed by the histopathological examination. The results all together denote the potential therapeutic value of ARBs therapy in osteoporosis.
最近，人们对 RAS 在控制炎症性骨疾病中的重要性给予了极大的关注，这是因为在骨骼组织中发现了其局部存在。研究发现，局部 RAS 表达于成骨细胞和破骨细胞上，并通过血管紧张素 II（AngII）受体发挥作用，包括血管紧张素 II 型 1 受体（AT R）和血管紧张素 II 型 2 受体。替米沙坦（TLM）是一种 AT R 阻滞剂（ARB），本研究旨在探讨其对骨质疏松症大鼠骨健康的治疗作用。以 200mg/kg/天/腹腔注射的剂量使用半乳糖作为还原糖来诱导雄性大鼠骨质疏松症。以 5mg/kg/天的剂量给骨质疏松症大鼠口服 TLM 连续四周。估计胫骨和股骨骨密度，测量血清骨形成和骨吸收生物标志物水平，评估血液中的矿物质含量，最后确定骨细胞外调节激酶（ERK）的表达。TLM 显著改善了半乳糖对骨密度的有害影响。它抑制了血清骨特异性碱性磷酸酶和骨钙素，同时升高了血清骨保护素（OPG）。另一方面，TLM 抑制了血清核因子-κβ受体激活剂配体（RANKL）、抗酒石酸酸性磷酸酶和组织蛋白酶 K 的明显升高。此外，它显著抑制了骨细胞中 ERK 的表达，从而阻止了破骨细胞的生成。AT R 抑制消除了血清钙和磷的升高，并使血清超氧化物歧化酶和过氧化氢酶正常化。这些 TLM 在半乳糖处理大鼠中的保护作用通过组织病理学检查得到证实。所有结果都表明 ARB 治疗在骨质疏松症中的潜在治疗价值。
