Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186; Hard-tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju 61186, Korea.
Gyeongnam Biohealth Research Center, Gyeongnam Branch Institute, Korea Institute of Toxicology, Jinju 52834, Korea.
BMB Rep. 2023 Oct;56(10):545-550. doi: 10.5483/BMBRep.2023-0054.
Osteoporosis is a major public health concern, which requires novel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeutic agents due to their safety and efficacy. In this study, we investigated the regulatory activities of boeravinone B (BOB), a natural rotenoid isolated from the medicinal plant Boerhavia diffusa, on the differentiation of osteoclasts and mesenchymal stem cells (MSCs), the two main cell components responsible for bone remodeling. We found that BOB inhibited osteoclast differentiation and function, as determined by TRAP staining and pit formation assay, with no significant cytotoxicity. Furthermore, our results showing that BOB ameliorates ovariectomyinduced bone loss demonstrated that BOB is also effective in vivo. BOB exerted its inhibitory effects on osteoclastogenesis by downregulating the RANKL/RANK signaling pathways, including NF-κB, MAPK, and PI3K/Akt, resulting in the suppression of osteoclast-specific gene expression. Further experiments revealed that, at least phenomenologically, BOB promotes osteoblast differentiation of bone marrow-derived MSCs but inhibits their differentiation into adipocytes. In conclusion, our study demonstrates that BOB inhibits osteoclastogenesis and promotes osteoblastogenesis in vitro by regulating various signaling pathways. These findings suggest that BOB has potential value as a novel therapeutic agent for the prevention and treatment of osteoporosis. [BMB Reports 2023; 56(10): 545-550].
骨质疏松症是一个主要的公共卫生问题，需要新的治疗策略来预防或减轻骨质流失。由于其安全性和有效性，天然化合物作为潜在的治疗剂引起了人们的关注。在这项研究中，我们研究了来自药用植物 Boerhavia diffusa 的天然鱼藤酮 Boeravinone B（BOB）对破骨细胞和间充质干细胞（MSCs）分化的调节作用，这两种细胞是负责骨重塑的主要细胞成分。我们发现，BOB 通过 TRAP 染色和陷窝形成测定抑制破骨细胞分化和功能，且无明显细胞毒性。此外，我们的结果表明 BOB 改善卵巢切除诱导的骨丢失，表明 BOB 在体内也有效。BOB 通过下调 RANKL/RANK 信号通路，包括 NF-κB、MAPK 和 PI3K/Akt，抑制破骨细胞特异性基因表达，从而发挥其对破骨细胞生成的抑制作用。进一步的实验表明，至少从现象上看，BOB 促进骨髓来源的 MSCs 的成骨细胞分化，但抑制其向脂肪细胞分化。总之，本研究表明，BOB 通过调节各种信号通路在体外抑制破骨细胞生成并促进成骨细胞生成。这些发现表明，BOB 作为预防和治疗骨质疏松症的新型治疗剂具有潜在价值。[BMB 报告 2023；56(10):545-550]。
