Aged skin exacerbates experimental osteoarthritis via enhanced IL-36R signaling

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◆ 논문 초록 (Abstract)

Age-related inflammation plays a pivotal role in osteoarthritis (OA) pathogenesis, but the mechanism is not fully understood. Here, we identify decreased IL-36 receptor antagonists (IL-36Ra) in epidermal keratinocytes from a premature-aged skin mice model, aged mice and patients. Decreased IL-36Ra leads to increased secretion of IL-36 agonists to serum and joints, which activates proinflammatory signaling and promotes senescence in chondrocytes and synovial fibroblasts, thereby aggravates OA progression. Deletion of IL-36Ra in keratinocytes exacerbates, whereas intra-articular inhibition of IL-36R signaling effectively attenuates OA progression in male mice. Moreover, we also generate microneedles loaded with mouse recombinant IL-36Ra protein or spesolimab, insert them directly into skin to sustainably inhibit IL-36R signaling, which both clearly attenuate 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, and targeting IL-36R signaling in aged skin with microneedles represents a promising disease-modifying approach.

◆ 원문 정보
저자: Chen D, Wang C, Yang C, Cheng Q, Chen L et al.
저널: Nat Commun
연도: 2026
DOI: 10.1038/s41467-026-68399-z

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