PRMT7介导的PTEN激活增强雌性小鼠的骨再生。

PRMT7-Mediated PTEN Activation Enhances Bone Regeneration in Female Mice.

作者信息

Zhang Yingfei, Qing Jia, Li Yang, Gao Xin, Lu Dazhuang, Wang Yiyang, Gu Lanxin, Zhang Hui, Li Zechuan, Wang Xu, Zhou Yongsheng, Zhang Ping

机构信息

Department of Prosthodontics, Peking University Hospital of Stomatology, Beijing 100081, China.

National Clinical Research Center for Oral Diseases, Peking University Hospital of Stomatology, Beijing 100081, China.

出版信息

Int J Mol Sci. 2025 Mar 25;26(7):2981. doi: 10.3390/ijms26072981.

DOI:10.3390/ijms26072981

PMID:40243588

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11988880/

Abstract

Epigenetic regulation provides new insights into the mechanisms of osteogenic differentiation and identifies potential targets for treating bone-related diseases. However, the specific regulatory networks and mechanisms involved still need further investigation. In this study, we identify PRMT7 as a novel epigenetic regulator of mesenchymal stem cells (MSCs) osteogenic commitment. Conditional knockout of in mice reveals a significant impairment in osteogenesis and bone regeneration, specifically in females, affecting both femurs and mandibles, with no noticeable effect in males. Mechanistically, PRMT7 modulates MSCs osteogenic differentiation by activating PTEN. Specifically, PRMT7 enhances PTEN transcription by increasing H3R2me1 levels at the PTEN promoter. Additionally, PRMT7 interacts with the PTEN protein and stabilizes nuclear PTEN, revealing an unprecedented pathway. Notably, overexpression of PTEN alleviates the osteogenic deficits observed in -deficient mice. This research establishes PRMT7 as a potential therapeutic target for promoting bone formation/regeneration and offers novel molecular insights into the PRMT7-PTEN regulatory axis, underscoring its significance in bone biology and regenerative medicine.

摘要

表观遗传调控为成骨分化机制提供了新的见解，并确定了治疗骨相关疾病的潜在靶点。然而，所涉及的具体调控网络和机制仍需进一步研究。在本研究中，我们确定PRMT7是间充质干细胞（MSC）成骨定向的一种新型表观遗传调节因子。在小鼠中条件性敲除PRMT7揭示了成骨和骨再生的显著受损，特别是在雌性中，影响股骨和下颌骨，而在雄性中没有明显影响。从机制上讲，PRMT7通过激活PTEN来调节MSC的成骨分化。具体而言，PRMT7通过增加PTEN启动子处的H3R2me1水平来增强PTEN转录。此外，PRMT7与PTEN蛋白相互作用并稳定核PTEN，揭示了一条前所未有的途径。值得注意的是，PTEN的过表达减轻了在PRMT7缺陷小鼠中观察到的成骨缺陷。这项研究将PRMT7确立为促进骨形成/再生的潜在治疗靶点，并为PRMT7-PTEN调控轴提供了新的分子见解，强调了其在骨生物学和再生医学中的重要性。