Department of Pharmacology, The Public Service Platform of South China Sea for R&D Marine Biomedicine Resources, Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, People's Republic of China.
Department of Stomatology, Guangdong Medical University, Zhanjiang, People's Republic of China.
Calcif Tissue Int. 2019 Nov;105(5):531-545. doi: 10.1007/s00223-019-00596-z. Epub 2019 Aug 21.
Anti-resorptive agents like bisphosphonates have been widely used for the treatment of postmenopausal osteoporosis. However, their long-term safety and efficacy are still controversial. This study is to examine the effect of Asiatic acid (AA) in osteoclastic differentiation, and further to investigate its effect on bone quality in animals. Effect of AA on osteoclastic differentiation was measured by Tartrate-resistant acid phosphatase stain, bone resorption pit assays, and quantitative real-time polymerase chain reaction. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor-β (TGF-β) signaling were measured by western blot before and after AA treatment. Ovariectomized (OVX) wild-type or Smad7 partially knock out mice were used to evaluate the effects of AA on bone quality by micro-computed tomography, mechanical test, and histomorphometry. Results revealed a dose-dependent inhibitory effect of AA on osteoclastic differentiation. After AA treatment, Smad7 was upregulated, while NF-κB and TGF-β signaling were inhibited during osteoclastic differentiation. Results from animal study revealed that AA prevented bone from further loss caused by OVX and increased the mechanical properties of femur in wild-type animals. AA also prevented bone loss in the Smad7-deficient animals. When combining with OVX in the Smad7-deficient mice, AA could only partially preserve their bone mass. Taken together, we found that AA effectively inhibited osteoclastic differentiation and attenuated osteoporosis, which effects may be through TGF-β and NF-κB pathways. This study reveals that AA may be a potential anti-resorptive agent for postmenopausal osteoporosis.
抗吸收剂如双磷酸盐已被广泛用于治疗绝经后骨质疏松症。然而，它们的长期安全性和疗效仍存在争议。本研究旨在研究齐墩果酸（AA）对破骨细胞分化的影响，并进一步研究其对动物骨质量的影响。通过抗酒石酸酸性磷酸酶染色、骨吸收陷窝试验和实时定量聚合酶链反应测定 AA 对破骨细胞分化的影响。用 Western blot 法测定 AA 处理前后核因子κB（NF-κB）和转化生长因子-β（TGF-β）信号。用卵巢切除（OVX）野生型或 Smad7 部分敲除小鼠评估 AA 对骨质量的影响，通过微计算机断层扫描、力学试验和组织形态计量学进行评估。结果显示 AA 对破骨细胞分化有剂量依赖性抑制作用。AA 处理后，Smad7 上调，而 NF-κB 和 TGF-β信号在破骨细胞分化过程中被抑制。动物研究结果表明，AA 可防止 OVX 引起的骨进一步丢失，并增加野生型动物股骨的力学性能。AA 还可防止 Smad7 缺陷型动物的骨丢失。当在 Smad7 缺陷型小鼠中与 OVX 联合使用时，AA 只能部分保留其骨量。总之，我们发现 AA 能有效抑制破骨细胞分化，减轻骨质疏松症，其作用可能通过 TGF-β和 NF-κB 途径。本研究表明 AA 可能是一种治疗绝经后骨质疏松症的潜在抗吸收剂。
