School of Clinical Medicine, Weifang Medical University, Weifang 261053, China.
Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250013, China.
Biochem Pharmacol. 2023 May;211:115516. doi: 10.1016/j.bcp.2023.115516. Epub 2023 Mar 24.
Osteoporosis is a common inflammaging-related condition, where long-term accumulation of pro-inflammatory cytokines causes massive bone loss. Periplocin, a cardiotonic steroid isolated from Periploca forrestii, has been proved to reduce inflammation in several inflammatory diseases, such as rheumatoid arthritis. However, its effect and mechanism of inflammation in osteoporosis, in which pro-inflammatory factors accelerate bone loss, has not been well demonstrated. In this study, periplocin attenuated receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation of bone marrow-derived macrophages (BMMs) and RAW264.7 cells in vitro. It reduced osteoclast numbers and bone resorption in a concentration- and time-dependent manner. Further, periplocin treatment resulted in reduced bone loss on mice with ovariectomy-induced osteoporosis in vivo. By transcriptome sequencing, periplocin was indicated to function through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways and attenuating interactions between NF-κB and nuclear factor of activated T-cells 1 (NFATc1). It was further detected to bind low density lipoprotein receptor-related protein 4 (LRP4) in osteoclasts to exert anti-inflammatory and anti-osteoclastic effects. Overall, the findings have highlighted a better understanding for the anti-inflammatory and anti-osteoclastic role of periplocin in osteoporosis and its mechanism, bringing new possibilities for osteoporosis treatment.
骨质疏松症是一种常见的与炎症衰老相关的疾病，长期积累的促炎细胞因子会导致大量骨质流失。从杠柳 Periploca forrestii 中分离出的强心甾苷，已被证明可减少几种炎症性疾病（如类风湿关节炎）中的炎症。然而，其在骨质疏松症中的炎症作用和机制，即促炎因子加速骨质流失，尚未得到充分证实。在这项研究中，杠柳苷在体外可减轻核因子-κB 受体激活剂配体（RANKL）诱导的骨髓来源巨噬细胞（BMM）和 RAW264.7 细胞的破骨细胞分化。它呈浓度和时间依赖性减少破骨细胞数量和骨吸收。此外，杠柳苷治疗可减少去卵巢诱导的骨质疏松症小鼠体内的骨丢失。通过转录组测序，杠柳苷通过抑制丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB）信号通路以及减轻 NF-κB 与活化 T 细胞核因子 1（NFATc1）之间的相互作用来发挥作用。进一步检测到它与破骨细胞中的低密度脂蛋白受体相关蛋白 4（LRP4）结合，发挥抗炎和抗破骨细胞作用。总的来说，这些发现使人们更好地理解了杠柳苷在骨质疏松症中的抗炎和抗破骨细胞作用及其机制，为骨质疏松症的治疗带来了新的可能性。
