Department of Molecular Medicine, Chonnam National University Graduate School, Gwangju, Korea.
Department of Oral Biochemistry, Dental Science Research Institute, Korea Mouse Phenotyping Center, School of Dentistry, Chonnam National University, Gwangju, Korea.
J Cell Mol Med. 2021 Feb;25(3):1425-1438. doi: 10.1111/jcmm.16228. Epub 2020 Dec 23.
The dynamic balance between bone formation and bone resorption is vital for the retention of bone mass. The abnormal activation of osteoclasts, unique cells that degrade the bone matrix, may result in many bone diseases such as osteoporosis. Osteoporosis, a bone metabolism disease, occurs when extreme osteoclast-mediated bone resorption outstrips osteoblast-related bone synthesis. Therefore, it is of great interest to identify agents that can regulate the activity of osteoclasts and prevent bone loss-induced bone diseases. In this study, we found that N-[2-(4-benzoyl-1-piperazinyl)phenyl]-2-(4-chlorophenoxy) acetamide (PPOAC-Bz) exerted a strong inhibitory effect on osteoclastogenesis. PPOAC-Bz altered the mRNA expressions of several osteoclast-specific marker genes and blocked the formation of mature osteoclasts, suppressing F-actin belt formation and bone resorption activity in vitro. In addition, PPOAC-Bz prevented OVX-induced bone loss in vivo. These findings highlighted the potential of PPOAC-Bz as a prospective drug for the treatment of osteolytic disorders.
骨形成和骨吸收之间的动态平衡对于维持骨量至关重要。破骨细胞的异常激活，即降解骨基质的独特细胞，可能导致许多骨骼疾病，如骨质疏松症。骨质疏松症是一种骨骼代谢疾病，当极端的破骨细胞介导的骨吸收超过成骨细胞相关的骨合成时就会发生。因此，寻找能够调节破骨细胞活性并预防因骨丢失引起的骨骼疾病的药物具有重要意义。在这项研究中，我们发现 N-[2-(4-苯甲酰基-1-哌嗪基)苯基]-2-(4-氯苯氧基)乙酰胺（PPOAC-Bz）对破骨细胞生成具有很强的抑制作用。PPOAC-Bz 改变了几个破骨细胞特异性标记基因的 mRNA 表达，并阻断了成熟破骨细胞的形成，抑制了体外 F-肌动蛋白带的形成和骨吸收活性。此外，PPOAC-Bz 预防了 OVX 诱导的体内骨丢失。这些发现强调了 PPOAC-Bz 作为一种治疗溶骨性疾病的潜在药物的潜力。
