Good news!
"... A joint research team ... has identified a key protein, SHP (NR0B2), that plays a critical protective role in cartilage and may offer a new therapeutic strategy for osteoarthritis. ...
The researchers first analyzed cartilage tissues from osteoarthritis patients and animal models of the disease. They found that the levels of SHP protein decreased significantly as the disease progressed, suggesting that loss of this protective factor contributes to accelerated cartilage destruction.
Further experiments showed that mice lacking SHP experienced more severe pain and faster cartilage degradation compared to normal mice. In contrast, restoring SHP levels in the joints led to reduced cartilage damage and improved joint function. ..."
From the 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."
Small heterodimer partner protects against osteoarthritis by inhibiting IKKβ/NF-κB-mediated matrix-degrading enzymes in chondrocytes (open access, but limited to preprint)
Schematic illustration of SHP (NR0B2)-mediated protection against osteoarthritis.
No comments:
Post a Comment