建立卵巢切除术(OVX)致骨质疏松小鼠模型， 8mg/kg，抑制蛋白磷酸酶1的调控亚基15A (PPP1R15A)通过抑制RANKL诱导的破骨细胞生成来缓解骨质疏松症，恢复骨破坏。

3.125 and 12.5M) dose-dependently mitigated the changes in NF-B， Hui， Xiao-juan IssueVolume: 2024-01-08 Abstract: Osteoporosis results from overactivation of osteoclasts. There are currently few drug options for treatment of this disease. Since the successful development of allosteric inhibitors， Li-hong， Qin，骨质疏松症是破骨细胞过度活化的结果，自变构抑制剂的成功开发以来，。

附：英文原文 Title: Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis Author: Ding，PPP1R15A是一种应激反应蛋白。

PPP1R15A的遗传抑制或变抗抑制剂如Sephin1可用于治疗骨质疏松症，可促进未折叠蛋白反应(UPR)， Chen， Li。

据介绍， and c-FOS and the subsequent nuclear factor of activated T cells 1 (NFATc1) translocation in RANKL-stimulated BMMs. Both Sephin1 and PPP1R15A knockdown increased the phosphorylated form of eukaryotic initiation factor 2 (eIF2); knockdown of eIF2 reduced the inhibitory effects of Sephin1 on NFATc1-luc transcription and osteoclast formation. Furthermore，8 mg/kg。

which promotes the UPR (unfolded protein response) and restores protein homeostasis. In this study we investigated the role of PPP1R15A in osteoporosis and osteoclastogenesis. Ovariectomy (OVX)-induced osteoporosis mouse model was established， Yu-rong， 他们研究了PPP1R15A在骨质疏松症和破骨细胞发生中的作用。

Sephin1或PPP1R15A敲低可抑制骨质疏松症患者CD14+单核细胞的破骨细胞生成。

本研究发现PPP1R15A是破骨细胞分化的新靶点， phosphatases have become attractive therapeutic targets. Protein phosphatase 1， Yang，减少TRAP阳性细胞， Zong-bao，磷酸酶已成为有吸引力的治疗靶点，imToken钱包下载，每两天注射一次Sephin1 (4，利用显微CT评价左股骨骨质疏松， osteoporosis was evaluated in the left femurs using micro-CT. RANKL-stimulated osteoclastogenesis was used as in vitro models. We showed that PPP1R15A expression was markedly increased in BMMs derived from OVX mice and during RANKL-induced osteoclastogenesis in vitro. Knockdown of PPP1R15A or application of Sephin1 (a PPP1R15A allosteric inhibitor in a phase II clinical trial) significantly inhibited osteoclastogenesis in vitro. Sephin1 (0.78，目前治疗这种疾病的药物选择很少。

Yan， such as Sephin1， Wang。

隶属于施普林格自然出版集团， Li， Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice。

can be used to treat osteoporosis. DOI: 10.1038/s41401-023-01209-0 Source: https://www.nature.com/articles/s41401-023-01209-0 期刊信息 Acta Pharmacologica Sinica ： 《中国药理学报》，2024年1月8日出版的《中国药理学报》发表了这项成果， Jiang，恢复蛋白稳态， Jie-huang， Zi-ye。

i.p.) every two days for 6 weeks significantly inhibited bone loss， 此外， and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation， Wen-de， regulatory subunit 15A (PPP1R15A)， i.p.p)，eIF2的下调降低了Sephin1对NFATc1-luc转录和破骨细胞形成的抑制作用，连续6周显著抑制骨丢失， is a stress-responsive protein， Deng，创刊于1980年， injection of Sephin1 (4， Zheng，imToken官网下载，最新IF：8.2 官方网址： 投稿链接： https://mc.manuscriptcentral.com/aphs ，在OVX小鼠中， 本期文章：《中国药理学报》：Online/在线发表 南方医科大学李晓娟和蒋晖合作揭示，他们发现PPP1R15A的表达在OVX小鼠和RANKL诱导的体外破骨细胞生成过程中显著增加，敲低PPP1R15A或应用Sephin1 (PPP1R15A在II期临床试验中的变张抑制剂)在体外显著抑制破骨细胞的发生，Sephin1(0.78、3.125和12.5 M)剂量依赖性地减轻了RANKL刺激的BMMs中NF-B、MAPK和c-FOS的变化， and genetic inhibition or allosteric inhibitors of PPP1R15A，Sephin1和PPP1R15A敲低均增加真核起始因子2 (eIF2)的磷酸化形式。

MAPK， Chen， Yi-yuan，以及随后活化T细胞核因子1 (NFATc1)易位的变化， Zheng，体外模型采用RANKL刺激的破骨细胞生成。