Targeting neuregulin-1 in cartilage homeostasis restoration: Kaempferol-3-o-rutinoside as a novel treatment for osteoarthritis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Osteoarthritis (OA) is a progressive degenerative joint disease with no effective cure. Although Kaempferol-3-O-rutinoside (KR), a naturally occurring flavonoid glycoside, has demonstrated antioxidant and anti-inflammatory effects, however, its therapeutic potential in OA remains unexplored. Purpose This study aimed to investigate the chondroprotective and subchondral bone-preserving effects of KR in OA and to elucidate its underlying molecular mechanisms. Design We assessed the effects of KR on chondrocyte viability, apoptosis, and the expression of inflammatory and catabolic mediators (MMP-13, ADAMTS5), as well as on anabolic markers in vitro. Chondrogenic differentiation was evaluated in adipose-derived mesenchymal stem cells (ADMSCs). We examined the in vivo efficacy of KR using a murine model of OA induced by anterior cruciate ligament transection (ACLT). Treatment outcomes were assessed based on Osteoarthritis Research Society International (OARSI) scoring and subchondral bone microstructural analysis. Finally, we performed mechanistic studies employing RNA sequencing, siRNA-mediated knockdown, and co-immunoprecipitation assays. Results We found that KR enhanced chondrocyte viability, suppressed apoptosis, downregulated inflammatory and catabolic mediators, and upregulated anabolic marker expression in vitro. KR also promoted chondrogenesis in ADMSCs and improv

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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