Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Jiawei Lu, Qi He, Huan Wang, Lutian Yao, Michael Duffy, Hanli Guo, Corben Braun, Yilu Zhou, Qiushi Liang, Yuewei Lin, Shovik Bandyopadhyay, Kai Tan, Yongwen Choi, X. Sherry Liu, Ling Qin
{"title":"Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice","authors":"Jiawei Lu, Qi He, Huan Wang, Lutian Yao, Michael Duffy, Hanli Guo, Corben Braun, Yilu Zhou, Qiushi Liang, Yuewei Lin, Shovik Bandyopadhyay, Kai Tan, Yongwen Choi, X. Sherry Liu, Ling Qin","doi":"10.1038/s41413-025-00405-4","DOIUrl":null,"url":null,"abstract":"<p>Bone resorption by osteoclasts is a critical step in bone remodeling, a process important for maintaining bone homeostasis and repairing injured bone. We previously identified a bone marrow mesenchymal subpopulation, marrow adipogenic lineage precursors (MALPs), and showed that its production of RANKL stimulates bone resorption in young mice using <i>Adipoq-Cre</i>. To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone, we generated inducible reporter mice (<i>Adipoq-CreER Tomato</i>) and RANKL deficient mice (<i>Adipoq-CreER RANKLflox/flox, iCKO</i>). Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq<sup>+</sup> cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation. In situ hybridization showed that <i>RANKL</i> mRNA is only detected in MALPs, but not in osteogenic cells. RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone. Ovariectomy (OVX) induced trabecular bone loss at both sites. RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass. Furthermore, bone healing after drill-hole injury was delayed in <i>iCKO</i> mice. Together, our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis, postmenopausal bone loss, and injury repair.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"183 1","pages":""},"PeriodicalIF":14.3000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bone Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41413-025-00405-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

Abstract

Bone resorption by osteoclasts is a critical step in bone remodeling, a process important for maintaining bone homeostasis and repairing injured bone. We previously identified a bone marrow mesenchymal subpopulation, marrow adipogenic lineage precursors (MALPs), and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre. To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone, we generated inducible reporter mice (Adipoq-CreER Tomato) and RANKL deficient mice (Adipoq-CreER RANKLflox/flox, iCKO). Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+ cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation. In situ hybridization showed that RANKL mRNA is only detected in MALPs, but not in osteogenic cells. RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone. Ovariectomy (OVX) induced trabecular bone loss at both sites. RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass. Furthermore, bone healing after drill-hole injury was delayed in iCKO mice. Together, our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis, postmenopausal bone loss, and injury repair.

Abstract Image

骨髓成脂谱系前体是成年小鼠骨吸收的主要调节因子
破骨细胞的骨吸收是骨重塑的关键步骤,是维持骨稳态和修复损伤骨的重要过程。我们之前确定了骨髓间充质亚群,骨髓脂肪生成谱系前体(MALPs),并表明其产生的RANKL刺激了使用Adipoq-Cre的年轻小鼠的骨吸收。为了排除发育缺陷并研究malps衍生的RANKL在成人骨骼中的作用,我们建立了诱导型报告小鼠(Adipoq-CreER Tomato)和RANKL缺陷小鼠(Adipoq-CreER RANKLflox/flox, iCKO)。单细胞- rna测序数据分析和谱系追踪显示,Adipoq+细胞不仅含有malp,还含有一些能够成骨分化的间充质祖细胞。原位杂交显示RANKL mRNA仅在malp中检测到,而在成骨细胞中未检测到。3月龄MALPs RANKL缺失导致长骨和椎骨骨小梁骨量迅速增加,原因是骨吸收减少,但对皮质骨没有影响。卵巢切除术(OVX)导致两个部位的小梁骨丢失。OVX治疗前或OVX治疗后6周,RANKL耗损可保护和恢复小梁骨量。此外,iCKO小鼠钻孔损伤后骨愈合延迟。总之,我们的研究结果表明,malp在控制小梁骨吸收中起主导作用,来自malp的RANKL对于成人骨稳态、绝经后骨质流失和损伤修复中的小梁骨转换至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信