P7C3 Ameliorates Bone Loss by Inhibiting Osteoclast Differentiation and Promoting Osteogenesis.
P7C3 Ameliorates Bone Loss by Inhibiting Osteoclast Differentiation and Promoting Osteogenesis.
复制标题
P7C3通过抑制破骨细胞分化和促进成骨来改善骨丢失。
作者：
骨稳态，即骨吸收和骨形成之间的平衡，对维持成年人健康的骨组织至关重要。这一过程的中断可能导致骨质疏松症等病理情况。双靶点药物能够抑制过度的骨吸收和刺激骨形成，正在被探索为开发治疗骨质疏松症的新方法的一种有前途的策略。在本研究中，我们研究了P7C3对骨重建的影响及其在治疗骨质疏松症中的潜在作用。特别是，P7C3通过AKT-NF-κB-NFATc1信号通路显著抑制核因子-κB受体激活剂配体(RANKL)诱导的骨髓巨噬细胞破骨细胞分化。此外，RNAseq分析表明，P7C3通过Wnt/β-catenin信号通路促进成骨细胞的分化和功能，从而促进骨形成。此外，μCT分析和对P7C3处理的小鼠骨组织的组织学检查显示，钛诱导的骨侵蚀和卵巢切除引起的骨丢失都有所减轻。提示P7C3可能在骨重建中具有新的功能，有望成为治疗骨质疏松症的药物。©2023作者。JBMR Plus由威利期刊有限责任公司代表美国骨骼和矿物研究学会出版。保持骨骼动态平衡对成年人健康的骨组织至关重要，而骨质破坏会导致骨质疏松症。抑制过度吸收和促进形成的双靶点制剂正在被探索为新的骨质疏松症治疗方法。研究P7C3对小鼠骨重建的影响及其对骨质疏松症的潜在治疗作用。P7C3通过Akt-NF-κB-NFATc1信号通路抑制破骨细胞分化，通过Wnt/β-catenin途径促进成骨细胞分化，促进骨形成。P7C3可能在治疗骨质疏松症方面具有潜在的治疗作用。
Bone homeostasis, the equilibrium between bone resorption and formation, is essential for maintaining healthy bone tissue in adult humans. Disruptions of this process can lead to pathological conditions such as osteoporosis. Dual‐targeted agents, capable of inhibiting excessive bone resorption and stimulating bone formation, are being explored as a promising strategy for developing new treatments to address osteoporosis. In this study, we investigated the effects of P7C3 on bone remodeling and its potential therapeutic role in osteoporosis treatment in mice. Specifically, P7C3 can remarkably suppress receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast differentiation in bone marrow macrophages via the Akt‐NF‐κB‐NFATc1 signaling pathway. Additionally, RNA sequencing (RNAseq) analysis revealed that P7C3 promoted osteoblast differentiation and function through the Wnt/β‐catenin signaling pathway, thereby enhancing bone formation. Furthermore, μCT analysis and histological examination of bone tissues from P7C3‐treated mice showed attenuation of both Ti‐induced bone erosion and ovariectomy (OVX)‐induced bone loss. These findings suggest that P7C3 may have a novel function in bone remodeling and may be a promising therapeutic agent for the treatment of osteoporosis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Maintaining bone homeostasis is crucial for healthy bone tissue in adults, and disruptions can cause osteoporosis. Dual‐targeted agents that inhibit excessive resorption and promote formation are being explored as new osteoporosis treatments. P7C3 was investigated on bone remodeling in mice and its potential therapeutic role in osteoporosis. P7C3 remarkably suppressed osteoclast differentiation through the Akt‐NF‐κB‐NFATc1 signaling pathway and promoted osteoblast differentiation through the Wnt/β‐catenin pathway, enhancing bone formation. P7C3 may have a promising therapeutic role in treating osteoporosis.
登录
查看更多内容
影响因子：
15
作者：
MacMillan KS;Naidoo J;Liang J;Melito L;Williams NS;Morlock L;Huntington PJ;Estill SJ;Longgood J;Becker GL;McKnight SL;Pieper AA;De Brabander JK;Ready JM
通讯作者：
Ready JM
DOI：
10.1056/nejmoa1916525
发表时间：
2020-08-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
通讯作者：
--
转移抑制因子 1 通过调节 Src-Wnt/β-catenin 信号传导控制成骨细胞分化和骨稳态
影响因子：
8
作者：
Chen, Meng;Shan, Liying;Wang, Baoli
通讯作者：
Wang, Baoli
影响因子：
17.1
作者：
Adam, Susanne;Simon, Nils;Hueber, Axel J.
通讯作者：
Hueber, Axel J.
阻断 PI3K/AKT 信号传导可抑制软骨下骨的骨硬化并减轻创伤后骨关节炎
影响因子：
5.6
作者：
Lin, Chuangxin;Shao, Yan;Xian, Cory J.
通讯作者：
Xian, Cory J.