PXD046993-1

PXD046993 is an original dataset announced via ProteomeXchange.

Title	Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3
Description	Cartilage aging is a quintessential feature of knee osteoarthritis, and extracellular matrix (ECM) stiffening is a typical feature of cartilage aging. However, the mechanism of ECM stiffening to influence chondrocytes and downstream molecules is still poorly understood. Here, we mimicked the physiological and pathological stiffness of human cartilage by using polydimethylsiloxane-based substrates. We show that the epigenetic regulation of Parkin by histone deacetylase 3 (HDAC3) represents a new mechanosensitive mechanism by which the stiff matrix affects the physiology of chondrocytes. We found that ECM stiffening could accelerate the senescence of cultured chondrocytes in vitro, and also found that stiff ECM downregulated HDAC3, drove Parkin acetylation to activate excessive mitophagy, and accelerated chondrocyte senescence and osteoarthritis in mice. In contrast, intra-articular injection of adeno-associated virus expressing HDAC3 restored the young phenotype of aged chondrocytes stimulated by ECM stiffening and alleviated osteoarthritis in mice. Our findings indicate that changes in the mechanical properties of ECM initiate pathogenic mechanotransduction signals, promote the acetylation of Parkin and hyperactivate mitophagy, and damage the health of chondrocytes. These findings may provide new insights into how the mechanical properties of ECM regulate chondrocytes.
HostingRepository	PRIDE
AnnounceDate	2024-06-16
AnnouncementXML	Submission_2024-06-16_14:35:31.286.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	lp wang
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-15 08:32:30	ID requested
⏵ 1	2024-06-16 14:35:32	announced
2	2024-10-22 06:46:04	announced	2024-10-22: Updated project metadata.

Fu B, Shen J, Zou X, Sun N, Zhang Z, Liu Z, Zeng C, Liu H, Huang W, Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3. Bone Res, 12(1):32(2024) [pubmed]

10.1038/s41413-024-00333-9;

submitter keyword: cartilago articularis，Matrix stiffness，osteoarthritis

bowen fu
contact affiliation	Guangdong Medical Innovation Platform for Translation of 3D Printing Application, The third Affiliated Hospital of Southern Medical University
contact email	371880012@qq.com
lab head
lp wang
contact affiliation	pgem-bio
contact email	wanglinpeng1412@163.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD046993

PRIDE project URI

• PRIDE
  1. PXD046993
     1. Label: PRIDE project
     2. Name: Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3