Small heterodimer partner protects against osteoarthritis by inhibiting IKKβ and NF-κB-mediated matrix-degrading enzymes in chondrocytes

Authors
Kang, Eun-Jung, Noh, Jung-Ran, Kim, Jae-Hoon, Park, Ji Ah, Ahn, Jeong-Pin, Kim, Min-Chan, Choi, Jung Hyeon, Choi, Young-Keun, Lee, In-Bok, Choi, Dong-Hee, Seo, Yun Jeong, Jung, Yoon Seok, Kim, Kyoung-Shim, Hwang, Jung Hwan, Kim, Yong-Bum, Lee, Jong-Soo, Ku, Bon Jeong, Jeong, Jin-Ok, Choi, Hueng-Sik, Kim, Jinhyun, Kim, Yong-Hoon, Lee, Chul-Ho


Lab

Journal
Nature Communications

Abstract
Osteoarthritis (OA), characterised by cartilage destruction, is the most common degenerative joint disease. However, no effective disease-modifying OA therapy is currently available. Herein, we report orphan nuclear receptor small heterodimer partner (SHP, NR0B2) as a novel catabolic regulator of OA pathogenesis. NR0B2 expression was markedly downregulated in cartilage from patients with OA. Global or chondrocyte-specific Nr0b2 deletion in male mice exacerbated OA-related pain and structural changes following surgical destabilization of the medial meniscus, accompanied by increased matrix metalloproteinase (MMP)-3 and MMP-13 expression in chondrocytes. Conversely, adeno-associated virus-mediated Nr0b2 overexpression in knee joints of male mice protected against accelerated knee OA caused by Nr0b2 deficiency. Mechanistically, NR0B2 inhibited IKKβ kinase activity via IKK complex interaction, downregulating NF-κB signalling. Our results demonstrate that NR0B2 has a chondroprotective role in OA progression by regulating matrix-degrading enzymes in an IKKβ/NF-κB-dependent manner, and gene therapy targeting Nr0b2 may be a promising therapeutic strategy for OA. Osteoarthritis is a marked by cartilage loss and limited by the absence of effective disease modifying treatments. Here, the authors show that orphan nuclear receptor small heterodimer partner (SHP) protects cartilage by suppressing IKKβ dependent NF κB signaling, highlighting it as a potential therapeutic target.

Keywords/Topics
Chondrocytes; Osteoarthritis

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://www.nature.com/articles/s41467-026-69864-5

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Test d'agrippement

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