PXD063645

PXD063645 is an original dataset announced via ProteomeXchange.

Title	A cationic polymer drives glycosaminoglycan assembly and secretion for preclinical osteoarthritis therapy
Description	Osteoarthritis (OA) affects nearly 500 million people worldwide and is characterized by an irreversible loss of glycosaminoglycans (GAGs) at articular cartilage surfaces. Despite advances, preserving cartilage GAGs and controlling their turnover in living cells remain challenging. Based on the hypothesis that GAGs can interact with cationic molecules, we demonstrated a cost-effective strategy to increase human cartilage GAGs using a molecular machine hexadimethrine bromide (HDMBr). HDMBr promoted stem cell chondrogenesis by attracting pericellular GAGs and upregulating vesicle formation, leading to increased matrix secretion. To determine how HDMBr influenced cellular protein expression, we performed proteomics by mass spectrometry on cultured human mesenchymal stem cells. Based on the results, HDMBr induced widespread proteomic changes and might stimulate intracellular GAG metabolism, intracellular trafficking, and GAG secretion. The proteomics data were also consistent with the evaluation of HDMBr in two animal models. In a rabbit model of large cartilage defects, HDMBr promoted the intrinsic regeneration of GAG-rich hyaline-like cartilage and improved tissue integration. In a rat OA model, low-dose HDMBr treatment increased cartilage thickness, supported cartilage matrix homeostasis, and improved the efficiency of cell-based therapy, evidently slowing OA progression compared to other tested clinical treatments. Overall, this study introduces a cost-effective GAG manipulation approach to cartilage repair and joint preservation, offering new insights into the mechanisms of cell-material interactions.
HostingRepository	iProX
AnnounceDate	2025-05-01
AnnouncementXML	Submission_2025-05-14_20:53:25.933.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yishan Chen
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-06 06:42:11	ID requested
⏵ 1	2025-05-14 20:53:26	announced

Dataset with its publication pending

submitter keyword: osteoarthritis, glycosaminoglycan, cationic polymer

Hongwei Ouyang
contact affiliation	Zhejiang University
contact email	hwoy@zju.edu.cn
lab head
Yishan Chen
contact affiliation	Zhejiang University
contact email	YishanChen@intl.zju.edu.cn
dataset submitter

iProX dataset URI