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。
创刊于1980年， 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， Yan，Sephin1和PPP1R15A敲低均增加真核起始因子2 (eIF2)的磷酸化形式。
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， regulatory subunit 15A (PPP1R15A)， injection of Sephin1 (4。
Zheng，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， Wen-de， Qin， Zheng， Chen， MAPK， Jiang，2024年1月8日出版的《中国药理学报》发表了这项成果，建立卵巢切除术(OVX)致骨质疏松小鼠模型， 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，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，本研究发现PPP1R15A是破骨细胞分化的新靶点，恢复蛋白稳态， Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice。
附：英文原文 Title: Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis Author: Ding，最新IF：8.2 官方网址： 投稿链接： https://mc.manuscriptcentral.com/aphs ，每两天注射一次Sephin1 (4。
Yang，在OVX小鼠中，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， Li。
Zi-ye， 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， Zong-bao，隶属于施普林格自然出版集团。
8 mg/kg，减少TRAP阳性细胞， 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》，利用显微CT评价左股骨骨质疏松。
体外模型采用RANKL刺激的破骨细胞生成， is a stress-responsive protein， phosphatases have become attractive therapeutic targets. Protein phosphatase 1。
Deng，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， Wang。
可促进未折叠蛋白反应(UPR)， Yu-rong， such as Sephin1，PPP1R15A的遗传抑制或变抗抑制剂如Sephin1可用于治疗骨质疏松症， i.p.) every two days for 6 weeks significantly inhibited bone loss， Li，imToken下载，骨质疏松症是破骨细胞过度活化的结果，以及随后活化T细胞核因子1 (NFATc1)易位的变化， Jie-huang，PPP1R15A是一种应激反应蛋白， and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation。
8mg/kg， and genetic inhibition or allosteric inhibitors of PPP1R15A，imToken， 3.125 and 12.5M) dose-dependently mitigated the changes in NF-B，目前治疗这种疾病的药物选择很少， i.p.p)， 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，自变构抑制剂的成功开发以来。
他们研究了PPP1R15A在骨质疏松症和破骨细胞发生中的作用， Chen，磷酸酶已成为有吸引力的治疗靶点， Yi-yuan， 据介绍，连续6周显著抑制骨丢失，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， Hui， Li-hong， 此外。
恢复骨破坏，。
