It’s only a matter of time before people with osteoarthritis will be growing back cartilage by taking a pill instead of undergoing joint replacement surgeries.
Scientists have regrown cartilage not just in mice but in people with a groundbreaking research that can open the door to treating osteoarthritis without joint replacement.
In older mice, a single injection that blocks a protein tied to aging was able to reverse the normal loss of knee cartilage.
Even more striking, the same treatment prevented arthritis from forming after knee injuries similar to ACL tears.
Those kinds of injuries can occur in both competitive athletes and weekend exercisers.
The researchers also point out that a pill version of this treatment is already being tested in human clinical trials for age-related muscle weakness.
Human Cartilage Responded Too
Researchers tested human knee cartilage taken from joint replacement surgeries.
That tissue included both cartilage-producing cells, called chondrocytes, and the surrounding support structure of the joint.
After treatment, the samples began producing new, functional cartilage.
In other words, even cartilage taken from severely damaged joints still had the ability to respond.
A drug replacement for knee replacements?
Taken together, the results suggest that cartilage lost to aging or arthritis might one day be restored with either a targeted injection or a daily pill.
If the same effects hold up in people, it could significantly reduce the need for knee and hip replacement surgery, which is currently the last resort for advanced osteoarthritis.
Why Osteoarthritis Is So Hard to Treat
Right now, treatment options are limited. Most focus on managing pain (typically with painkillers but some patients also use ice, heat packs and knee braces) or surgically replacing damaged joints.
There are no approved drugs that actually stop or reverse the cartilage breakdown that drives the disease.
This new approach goes after the root cause instead of just the symptoms.
The Aging Enzyme Behind the Damage
The protein targeted in the study is called 15-PGDH.
Researchers describe it as a “gerozyme,” meaning, its levels rise as the body ages.
The same team first identified gerozymes in 2023 and showed that they play a role in the gradual decline of tissue function.
In earlier mouse studies, high levels of 15-PGDH were linked to age-related muscle weakness.
Blocking the enzyme increased muscle mass and endurance. Forcing young mice to make more of it caused their muscles to shrink.
The enzyme has also been linked to regeneration in bone, nerve and blood cells.
Why Cartilage Is Different from Other Tissues
In many tissues, repair depends on stem cells. Cartilage appears to work differently.
Instead of relying on stem cells, cartilage cells themselves change how their genes behave.
After treatment in this research, chondrocytes shifted into a more youthful state, allowing them to produce healthy cartilage again without any involvement from stem or progenitor cells.
In the study, the enzyme-blocking treatment regenerated cartilage to a degree beyond what has been reported for any other therapy or intervention.
The cartilage most affected by osteoarthritis is hyaline cartilage, also called articular cartilage.
This smooth, glossy tissue allows joints like the knees, hips, shoulders and ankles to move with minimal friction. That’s the type that was regenerated in this study.
Wouldn’t it be great if cartilage naturally grew back?
Imagine that: As cartilage suffers from wear and tear over time, new cartilage cells are formed, replacing it.
Knees, hips and shoulders would always be well-padded with this natural shock absorber.
In this remarkable scenario, nobody would ever get bone-on-bone arthritic disease.
Unfortunately, evolution never led to this automated recovery.
Osteoarthritis develops when joints are stressed by aging, injury or excess weight.
Chondrocytes start releasing inflammatory molecules and breaking down collagen, the protein that gives cartilage its strength.
As collagen breaks down, cartilage becomes thinner and weaker.
Swelling and pain follow. Under normal conditions, articular cartilage has very little ability to repair itself.
Connecting Aging Chemistry to Repair
Earlier work from the same lab showed that a molecule called prostaglandin E2 is essential for tissue repair. The enzyme 15-PGDH breaks it down.
By blocking 15-PGDH, prostaglandin E2 levels rise slightly, which previously helped repair muscle, nerve, bone, liver and blood tissue in mice.
This led researchers to ask whether the same mechanism could apply to cartilage.
When they compared young and old mouse cartilage, 15-PGDH levels were about twice as high in older knees.
Regrowing Cartilage in Older Mice
Researchers treated older mice with a small molecule that inhibits 15-PGDH.
Some received whole-body injections, while others received injections directly into the knee joint.
In both cases, cartilage that had thinned with age became thicker across the joint surface.
Tests confirmed the tissue was true hyaline cartilage, not the weaker fibrocartilage often seen after
What Human Samples Revealed
Cartilage taken from people undergoing knee replacement surgery showed similar changes after one week of treatment.
The tissue displayed fewer destructive cells, less expression of breakdown-related genes, and early signs of cartilage regeneration.
Researchers say this shift in thinking could lead to bigger clinical gains by reprogramming existing cells rather than trying to replace them.
Looking Ahead to Human Trials
Phase 1 trials of a 15-PGDH inhibitor for muscle weakness have already shown the drug to be safe and biologically active in healthy volunteers.
Nevertheless, it’ll be perhaps many years from now before this discovery leads to the elimination of joint replacement surgeries.
There was once a time when a broken hip meant a death sentence — well before the advent of total hip replacement.
The refinement of hip replacement surgery has saved countless lives, and other joint replacement procedures have given life back to sufferers of osteoarthritis.
As much as the godsend that implanting hardware into joints has been for tens of millions of people worldwide, it’s super exciting to think that maybe within a generation, a drug for growing cartilage will be so effective that joint replacements will be made obsolete.
The researchers hope trials will soon test whether their discovery can regenerate cartilage in people.
