A anti-aging injection could it save millions of people from going through the
knee prosthesis ? Stanford Medicine researchers describe a molecule that, in mice, regrows cartilage in aging joints. The idea seems almost too good to be true, as osteoarthritis of the knee remains today synonymous with pain and major operations.
Osteoarthritis is a joint disease characterized by breakdown of cartilage. It concerns 9 to 10 million people in France. Nearly a third of them are affected in the knee. No medication slows or reverses the disease: we treat the pain, then we operate. The study published in the journal
Science suggests, however, that a 15-PGDH inhibitorgiven orally or as a local injection, could regenerate the knee cartilage and prevent osteoarthritis after injury.
Blocking 15-PGDH, a miraculous anti-aging solution?
Osteoarthritis occurs when a joint is subjected to stress related to aging, injury or obesity. Chondrocytes (main cartilage cells) then begin to release pro-inflammatory molecules and degrade collagen, the main structural protein of cartilage. This leads to thinning of the cartilage while inflammation causes the swelling and pain characteristic of the disease. Under normal conditions, articular cartilage rarely regenerates. Although some populations of stem cells capable of generating cartilage have been identified in bone, their detection in articular cartilage has been unsuccessful.
Conversely, previous work has demonstrated that prostaglandin E2 is essential for muscle stem cell function. The 15-PGDH molecule degrades prostaglandin E2. Therefore, inhibiting 15-PGDH activity, or increasing prostaglandin E2 levels, promotes the regeneration of damaged muscle, nerve, bone, colon, liver and blood cells in young mice. The Stanford team wondered whether 15-PGDH might also play a similar role in the aging of cartilage and joints. They then realized that in aged mice, the protein 15-PGDHdescribed as a “gerozyme”, is twice as abundant in the cartilage of the knee as in young animals.
Regeneration of knee cartilage
By blocking this enzyme using a small molecule injected into the abdomen and then directly into the joint, the thinned cartilage began to thicken again over the entire surface. “The regeneration of cartilage to such a degree in aged mice surprised us. The effect was remarkable”said Professor Bhutani, associate professor of orthopedic surgery and author of the study.
The researchers also tested their treatment in a model of anterior cruciate ligament rupture, a classic sports injury. Injections twice a week for four weeks significantly reduced the appearance of osteoarthritis: the treated mice kept preserved cartilage and placed weight more easily on the affected paw. Cellular analysis shows that adult chondrocytes adopt a younger genetic profile, without using stem cells. On osteoarthritic knee cartilage taken during prostheses, a week of treatment also reduced markers of degradation and restarted the production of articular cartilage.
An anti-aging injection very different from current infiltrations
Today, people suffering fromosteoarthritis
of the knee mainly have analgesics, physiotherapy and intra-articular injections of corticosteroids or hyaluronic acid, sometimes platelet-rich plasma. These options provide relief, lubricate the joint and reduce inflammation, but do little to regrow cartilage. Hence the interest in an injection which would aim, this time, to modify the very course of the disease and no longer just to alleviate the symptoms.
In mouse experiments, the15-PGDH inhibitor On the contrary, it thickens the cartilage sustainably and reduces the pain associated with movements, which gives hope for a truly regenerative treatment if these results are confirmed in humans. “This mechanism is quite remarkable and has truly revolutionized our understanding of tissue regeneration.”said Professor Bhutani. “It is clear that a large number of cells already present in cartilage are changing their gene expression profiles. By targeting these cells for regeneration, we could have a greater overall clinical impact.”.
Not yet available: what patients need to know
For now, this anti-aging injection has only been tested in mice and on human cartilage in the laboratory. A related 15-PGDH inhibitor has completed a phase 1 trial against age-related muscle weakness, but no trials yet target knee osteoarthritis. Researchers point out that prostaglandin E2 is also involved in inflammation and pain, hence the warning against any self-injection of products purchased online.