Osteoarthritis is not wear and tear, but a legacy of 425 million years of evolution Bone-forming cartilage cells give us strength — but also osteoarthritis

26 May 2025

Osteoarthritis does not arise from wear and tear, that’s a persistent misconception. So what causes this condition, which affects 1.2 million people in the Netherlands? Peter van der Kraan of Radboud university medical center searches for answers in evolution. He suspects that misbehaving cartilage cells, which are very useful early in life, turn against us later on.

All animals with bones can develop osteoarthritis, a painful joint disease. In zebrafish, it affects the jaw, and last February, Burgers’ Zoo euthanized a 59-year-old elephant partly due to osteoarthritis in her foreleg. Birds, dogs, turtles, and mice also suffer from painful joints. Remarkably, osteoarthritis tends to occur at about two-thirds of the species’ expected lifespan: in humans around age 55, in mice after just 13 months.

The fact that mice develop osteoarthritis 54 years earlier than humans suggests that osteoarthritis is not caused by mechanical wear. That outdated idea still persists in the Netherlands. But what, then, is the real cause? Peter van der Kraan, professor of Experimental Rheumatology at Radboudumc, believes osteoarthritis is an aging-related disease tied to biological age — and he looks to evolution for the answer.

Strong jaws

'About 425 million years ago, fish swam in the ocean that had only cartilage', Van der Kraan explains. 'Until a particular type of cartilage cell started depositing bone. That gave those animals an enormous evolutionary advantage: they developed bony jaws that were much stronger and ideal for eating a wide range of plants and animals.' Bone formation helped survival and reproduction in early life, which steered evolution forward. These fish later gave rise to bony fish, amphibians, reptiles, birds, and mammals, including humans.

In evolutionary terms, bone was a major advantage. But according to Van der Kraan, that same bone formation turns against us later in life, causing osteoarthritis. And because reproduction typically no longer occurs at that age, this late-life downside has no impact on evolution. Van der Kraan: 'From an evolutionary point of view, the benefits of bone in youth outweigh the disadvantages in old age.'

Misbehaving cartilage cells

The culprits in osteoarthritis are certain cartilage cells that become active at the wrong time and in the wrong place. These cells create new blood vessels, break down cartilage, and replace it with bone. Early in life, when bones are still growing, this is useful. But later, these cartilage cells go off course and cause the hallmarks of osteoarthritis: disappearing cartilage, and new blood vessels and bone forming in the wrong places.

For years, people don’t notice these errant cartilage cells, but later, they experience pain. This results from changes in the bone and loss of cartilage, as well as joint inflammation. Today, 1.2 million people in the Netherlands suffer from this condition, and that number is expected to exceed 3 million by 2050 due to population aging.

Exercise as medicine

If osteoarthritis is an evolutionary legacy, does that mean we’re powerless against it? 'Definitely not', says Van der Kraan. 'Lifestyle plays a big role. People who eat healthily are less likely to develop osteoarthritis, while being overweight increases the risk. But the most important thing is to stay active, both before and after developing the condition. We used to think joints wore out from use and that this caused osteoarthritis, but we now know that’s incorrect. Movement actually helps prevent it.'

Exercise is helpful primarily because of a substance stored in our cartilage: TGF-β. This signaling molecule suppresses inflammation and keeps the cartilage cells that cause osteoarthritis in check. But here’s the catch, it’s only activated when cartilage is loaded, and that loading comes from physical activity. Therefore, sitting on the couch is not good.

Outdated theory

Still, movement can be difficult due to the pain osteoarthritis causes. 'That’s why painkillers are a key part of treatment', Van der Kraan explains. 'We also emphasize lifestyle: losing weight if necessary and staying physically active. In severe cases, doctors can replace a joint.'

There is currently no cure for osteoarthritis. However, large studies involving colchicine and an IL-1 inhibitor in other conditions suggest these medications might reduce osteoarthritis risk. Further research is underway. 'Now that we better understand the real cause of osteoarthritis, we can move past the outdated theory of wear and tear', says Van der Kraan. 'That allows us to develop targeted strategies for prevention, treatment, and improving quality of life for patients.'

About the publication

This theory on the cause of osteoarthritis is published in Osteoarthritis and Cartilage Open: Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy. Peter van der Kraan. DOI: 10.1016/j.ocarto.2025.100624

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