Researchers reveal novel mechanisms of how neuronal guidance factor Sema3A protects cartilage
image: Sema3A inhibits neurite growth and alleviates peripheral pain sensation in osteoarthritis.
Credit: SIAT
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 the process where both cartilage wear and abnormal nerve growth cause pain in the joint.
In a study published in Bone Research, a team led by Dr. YANG Fan from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, along with collaborators, uncovered a promising role for the neuronal guidance factor Semaphorin 3A (Sema3A) in significantly slowing the progression of knee osteoarthritis by inhibiting nerve infiltration and maintaining cartilage health.
Sema3A is a member of the Semaphorin family. It is a signaling molecule predominantly found in the nervous system and plays a key role in guiding the direction of neuronal axons. Researchers found that it has significant cartilage-protective effects in OA.
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, there was an increased nerve fiber infiltration into cartilage, exacerbating both cartilage degeneration and joint pain.
To validate the therapeutic potential of Sema3A, researchers conducted a series of experiments. In mouse models, injecting the Sema3A protein or boosting its levels via gene therapy significantly reduced cartilage degradation and effectively inhibited nerve invasion. 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 hyaluronic acid treatments in clinics.
Besides, researchers 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 suggested that Sema3A may play a crucial role in the therapeutic efficacy of PRP.
This study provides a novel biological therapeutic option to arrest chondrocyte degeneration.