Sema3A Signaling Molecule Offers Promising Cartilage Protection in Osteoarthritis

Osteoarthritis (OA) is a prevalent degenerative joint condition that primarily affects millions worldwide, often targeting the knee joint. The disease progresses as the cartilage deteriorates, leading to bone damage, persistent pain, swelling, and impaired mobility. A complex challenge in understanding OA involves the intertwined processes of cartilage breakdown and abnormal nerve growth within the joint, both contributing to the characteristic pain.

Recent research published in one Research, led by Dr. Yang Fan from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, sheds light on a potential therapeutic target—Semaphorin 3A (Sema3A). This molecule, part of the semaphorin family known for neuronal guidance functions, appears to play a crucial role in protecting cartilage by inhibiting nerve infiltration into joint tissues.

In the early phases of OA, Sema3A expression shows a transient increase but then declines with disease progression as cartilage cells are lost. Animal studies reveal that knocking out Sema3A in cartilage tissue results in increased nerve fiber infiltration, worsening cartilage degradation and increasing pain. Conversely, therapeutic interventions that boost Sema3A levels—via protein injections or gene therapy—in mice significantly slowed cartilage deterioration and reduced nerve invasion. Notably, these approaches yielded even more promising results in rhesus monkeys, surpassing the effectiveness of standard treatments like hyaluronic acid.

Furthermore, researchers identified that platelet-rich plasma (PRP), a common treatment for joint issues, contains high levels of Sema3A. A clinical trial demonstrated that PRP injections provided substantial pain relief and improved knee joint function in OA patients, highlighting Sema3A's role in the therapeutic effects of PRP.

This groundbreaking study suggests that boosting Sema3A activity could be a viable strategy to prevent or slow cartilage degeneration in osteoarthritis, offering hope for more effective treatments that address both cartilage health and nerve-related pain pathways. The insights gained pave the way for new biological therapies aimed at preserving joint integrity and relieving pain in OA patients.

Source: https://medicalxpress.com/news/2025-04-sema3a-molecule-significant-cartilage-effects.html