PXD062165

PXD062165 is an original dataset announced via ProteomeXchange.

Title	Aged skin exacerbates experimental osteoarthritis via enhanced IL-36R signaling
Description	Increasing evidence suggests that age-related inflammation plays a pivotal role in osteoarthritis (OA) pathogenesis, but the mechanism is not fully understood. Here, we demonstrate that skin aging is an important driver of experimental OA progression in male mice via enhanced IL-36 receptor (IL-36R) signaling. We identified decreased IL-36 receptor antagonists (IL-36Ra) in epidermal keratinocytes from a premature-aged skin mouse model, aged mice, and patients. Decreased IL-36Ra in aged keratinocytes leads to increased secretion of IL-36 agonists to serum and joints, which activates proinflammatory signaling and promotes senescence in chondrocytes and synovial fibroblasts, thus aggravated OA progression. Genetic deletion of IL-36Ra in keratinocytes exacerbates experimental and age-related OA in male mice, whereas intra-articular inhibition of IL-36R signaling effectively attenuated OA progression. Moreover, we also generated microneedles loaded with mouse recombinant IL-36Ra protein or spesolimab, inserted them directly into skin to sustainably inhibit IL-36R signaling in epidermal keratinocytes, which both clearly attenuated OA progression in male mice. Overall, our results reveal that IL-36 agonists are age-related systemic inflammatory factors released from skin to joints and contribute to OA development. IL-36Ra shows potential clinical translational value for OA treatment, and targeting IL-36R signaling in aged skin with microneedles represents a promising disease-modifying approach.
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-22_16:24:28.570.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	dalin chen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-24 02:55:10	ID requested
⏵ 1	2026-02-22 16:24:29	announced

10.1038/s41467-026-68399-z;

Chen D, Wang C, Yang C, Cheng Q, Chen L, Yang P, Zou Z, Wang Z, Li H, Xiao Y, Wu J, Ke E, Wang X, Huang B, Bai X, Li K, Aged skin exacerbates experimental osteoarthritis via enhanced IL-36R signaling. Nat Commun, 17(1):1695(2026) [pubmed]

submitter keyword: aged skin, IL-36 receptor antagonist,osteoarthritis, microneedles, senescent keratinocytes

Kai Li
contact affiliation	Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
contact email	lk516433415@smu.edu.cn
lab head
dalin chen
contact affiliation	Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
contact email	dalincc@smu.edu.cn
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/2026/02/PXD062165

PRIDE project URI

• PRIDE
  1. PXD062165
     1. Label: PRIDE project
     2. Name: Aged skin exacerbates experimental osteoarthritis via enhanced IL-36R signaling