PXD041145

PXD041145 is an original dataset announced via ProteomeXchange.

Title	SIRT2 regulates extracellular vesicle-mediated liver-bone communication
Description	The interplay between liver and bone metabolism remains largely uncharacterized. Here, we uncover a mechanism of liver-bone crosstalk regulated by hepatocyte SIRT2. We demonstrate that hepatocyte SIRT2 expression is increased in aged mice and elderly humans. Liver-specific SIRT2 deficiency inhibits osteoclastogenesis and alleviates bone loss in mouse models of osteoporosis. We identify leucine-rich alpha-2-glycoprotein 1 (LRG1) as a functional cargo in hepatocyte-derived small extracellular vesicles (sEVs). In SIRT2-deficient hepatocytes, LRG1 levels in hepatocyte-derived sEVs are upregulated, leading to increased transfer of LRG1-containing sEVs to bone marrow-derived monocytes (BMDMs) and in turn to inhibition of osteoclast differentiation via reduced nuclear translocation of NF-κB p65. Treatment with sEVs carrying high levels of LRG1 inhibits osteoclast differentiation in human BMDMs and in mice with osteoporosis, resulting in attenuated bone loss in mice. Furthermore, the plasma level of sEVs carrying LRG1 is positively correlated with bone mineral density in humans. Thus, drugs targeting hepatocyte-osteoclast communication may constitute a promising therapeutic strategy for primary osteoporosis
HostingRepository	iProX
AnnounceDate	2023-03-27
AnnouncementXML	Submission_2023-06-06_23:38:22.211.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Longshuai Lin
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-27 19:40:15	ID requested
1	2023-05-04 19:27:07	announced
⏵ 2	2023-06-06 23:38:24	announced	2023-06-07: Update publication information.

Lin L, Guo Z, He E, Long X, Wang D, Zhang Y, Guo W, Wei Q, He W, Wu W, Li J, Wo L, Hong D, Zheng J, He M, Zhao Q, SIRT2 regulates extracellular vesicle-mediated liver-bone communication. Nat Metab, 5(5):821-841(2023) [pubmed]

submitter keyword: extracellular vesicle, liver-bone communication, SIRT2, LRG1

Ming He
contact affiliation	Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine
contact email	heming@shsmu.edu.cn
lab head
Longshuai Lin
contact affiliation	Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
contact email	snow6lin@163.com
dataset submitter

iProX dataset URI