Osteoarthritis (OA), is a common degenerative joint disease that affects millions of people worldwide, particularly targets the knee joint. Over time, the cartilage within the joint wears down, leading to damage in the underlying bone and resulting in pain, inflammation, and reduced function. A key mystery of OA is pain from both cartilage wear and abnormal nerve growth in the joint, a process not fully understood.

Recently, a research team led by Dr. YANG Fan from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, along with collaborators, have uncovered a promising role for the neuroguidance factor Semaphorin 3A (Sema3A) in significantly slowing the progression of knee osteoarthritis by inhibiting nerve infiltration and maintaining cartilage health. 

The findings was published in Bone Research on Jan. 2. 

In this study, researchers found that Sema3A, a member of the Semaphorin family, has significant cartilage-protective effects in OA. Sema3A is a signaling molecule predominantly found in the nervous system and plays a key role in guiding the direction of neuronal axons. 

The experimental results showed that, in the early stage of OA progression, the expression of Sema3A undergoes a transiently increases, followed by a gradual decline as cartilage cells are lost. By knocking out Sema3A in chondrocytes within animal models, the research team observed an increased nerve fiber infiltration into cartilage, exacerbating both cartilage degeneration and joint pain.

To further validate the therapeutic potential of Sema3A, the research team conducted a series of experiments using mice and rhesus monkeys. 

In mouse models, injecting the Sema3A protein or boosting its levels via gene therapy significantly reduced cartilage degradation and effectively inhibited nerve invasion. In contrast, when Sema3A was blocked, the mice had more severe cartilage damage and pain symptoms. In rhesus monkeys, Sema3A gene therapy demonstrated even more significant protective effects on cartilage, outperforming the current use of hyaluronic acid treatments in clinics. 

The study further revealed that platelet-rich plasma (PRP) is abundant in Sema3A. In a randomized controlled trial, OA patients receiving PRP injections experienced marked pain relief and improved knee joint function. These findings suggest that Sema3A may play a crucial role in the therapeutic efficacy of PRP.

This research may provide a novel biological therapeutic option to arrest chondrocyte degeneration.

Sema3A inhibits neurite growth and alleviates peripheral pain sensation in osteoarthritis. (Image by SIAT)

Media Contact: LU Qun

Email: qun.lu@siat.ac.cn

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Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans