New Clinical Insights into Knee Osteoarthritis

Breaking the Cycle

Knee osteoarthritis (OA) has long been understood as a disease of “wear and tear,” driven by mechanical stress and cartilage degradation. However, emerging research reveals a more complex picture – one that implicates a self-perpetuating cycle of inflammation, abnormal blood vessel growth (angiogenesis), and new ingrowth of sensory nerves into areas of the joint not previously innervated. These underlying biological processes offer one reason why individuals with mild to moderate structural changes can experience significant pain and functional limitation.

🔄 The Inflammation–Angiogenesis–Pain Loop

When cartilage in the knee begins to break down, damaged cartilage activates the release of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and various interleukins as part of an innate immune response aimed at initiating repair. These signals lead to increased production of vascular endothelial growth factor (VEGF), which promotes angiogenesis – the growth of new blood vessels.

These newly formed vessels are immature, structurally abnormal and highly permeable, allowing immune cells and inflammatory mediators to infiltrate the joint more easily. This amplifies inflammation, which further damages the cartilage, feeding back into the same cytokine-driven process.

Following angiogenesis, neoinnervation into parts of the joint that were previously not innervated including subchondral bone and synovial lining occurs. This neoinnervation is driven by the same angiogenic signals, with these nerves relying on the neovessels for survival.

Synovial Inflammation: A Central Player in OA Progression and Pain

Synovial inflammation (synovitis) plays a pivotal role in both the progression of OA and the severity of symptoms. The presence and degree of synovitis in knee OA has been correlated with pain levels, highlighting its clinical relevance (Zhang et al., 2007). Synovitis is not merely a consequence of cartilage breakdown but actively drives further cartilage degradation and contributes to pain.

Recent imaging studies following genicular artery embolization (GAE) demonstrate a significant reduction in synovitis, supporting the therapeutic impact of targeting abnormal neovasculature. Ultrasound and MRI assessments have shown decreased synovitis post-GAE, correlating with clinical improvements in pain and function (Hindsø et al., 2024; Dablan et al., 2024).

🎯 Targeting the Pathological Cycle: Genicular Artery Embolization with Sakurabead

Building on this evolving understanding, genicular artery embolization (GAE) represents an innovative, minimally invasive approach to disrupt the pathological cycle driving knee OA. GAE directly targets the abnormal neovasculature that perpetuates ongoing inflammation and sensory nerve growth within the joint.

Our product, Sakurabead, is a resorbable embolic bead designed to temporarily occlude these neovessels by starving them of blood supply. This selective ischemia causes:

• Regression of immature, leaky blood vessels,
• Subsequent loss of the new sensory nerves (neoinnervation) that depend on these vessels,
• Interruption of the self-perpetuating inflammatory cycle.

By breaking the cycle of inflammation Sakurabead’s mechanism directly addresses the underlying biology rather than only symptom management.

This temporary vascular blockade allows the joint microenvironment to reset, reducing pain and inflammation, and potentially slowing disease progression.

Supporting Holistic Management of Knee OA

Pain in osteoarthritis is complex and multifactorial, influenced by mechanical, inflammatory, neurological, and psychosocial factors. Current first-line management for knee OA emphasizes maintaining a healthy weight and engaging in regular exercise, particularly strengthening of the lower limb muscles to improve joint stability and function.

We believe that by supporting effective pain relief, patients are better able to engage with these foundational health-promoting behaviours. This approach not only aims to improve knee health but also fosters sustainable lifestyle habits that enhance overall well-being.