Nav: Home

The evolution of arthritic knees

April 07, 2020

The human knee is a triumph of design. The joint, which evolved fairly rapidly from our common ancestor with the chimpanzee to accommodate our bipedalism, likely contributed to our success as a species. However, as modern medicine extends the human lifespan, our species have learned pain in the form of osteoarthritis that can accompany the locomotion of this biomechanical masterpiece.

In a new study of the genetic features that help make this sophisticated joint possible, an international team of researchers found that the regulatory switches involved in the development of the knee also play a role in osteoarthritis, a partially heritable disease that afflicts at least 250 million people worldwide. The findings are published in the journal Cell.

Terence D. Capellini, Richard B. Wolf Associate Professor in the Department of Human Evolutionary Biology and the paper's corresponding author, explained it in terms of the burden our knees literally endure:

"From an evolutionary standpoint, the primate knee went from something that accommodated the forces of walking on four legs to placing all the weight on two legs," he said. "Going from a quadruped to a biped changes the force distribution. All our weight is being transmitted through our hips and our knees down to our ankles. The cells in the joint and the shape of the joint had to change to accommodate those new forces."

With such a specific task - and limited by its origins in the older primate knee - the optimized bipedal knee developed what is known as a constrained morphology, that is, it did not allow much variation. "As you can imagine, when you're designing a part for an airplane, you don't want to stray too much," Capellini said.

To understand how this complex mechanism came to be, researchers looked for evidence of accelerated natural selection: the series of mutations that aided us in walking upright.

"We wanted to know whether or not we could see signs of ancient evolution - ancient selection - in the regions of the genome that specifically sculpt the knee," said Capellini. To do this, they searched for traces of specific regulatory switches, pieces of DNA "responsible for turning on and off the genetic material that make the knee a human knee."

What they found reflects what Capellini suggests is indicative of "positive selection" - evidence that this new knee gave the fledgling bipeds an evolutionary advantage. The highest functioning knees would have been selected, reducing variation in knee shape over time by decreasing the genetic variation in the switches that control the joint's formation. What variation persisted likely didn't substantially matter at that time.

"Later, as human populations expand and drift, you start getting these genetic variants that slightly modify how the knee is shaped or how the knee is maintained," explained Daniel Richard, a Ph.D. candidate in human evolutionary biology and lead author on the paper. "Those slight deviations, acting on this constrained knee, lead to risk for developing osteoarthritis."

Those traits did not affect the success of the bipedal knee because natural selection promotes traits that allow individuals to reach sexual maturity and successfully breed. In essence, because this new knee gave young adults an edge on passing on their genetic material, it continued despite these variants. Our eventual old age had little role in its selection.

"We think that these slight modifications don't so much impact early life," said Richard. "But when you keep on walking up until you're 50 or 60, over that longer time span a super small change in your knee compounds over decades. Eventually it contributes to osteoarthritis disease in the elderly."

As a proof of principle, Capellini and colleagues performed two additional experiments. By studying the knee switches in patients with osteoarthritis compared to the general population, they found that osteoarthritis patients have on average more genetic variants in switches than those who don't have the disease. They also focused on a gene called GDF5 (Growth Differentiation Factor Five) that contributes to osteoarthritis risk in Europeans and Asians. Using CRISPR editing in mice and human cells, they pinpointed a genetic variant, present in billions of people, that effects the function of a key knee switch, thus changing knee shape and increasing osteoarthritis risk.

The stiffness and soreness humans feel today, therefore, may simply have piggybacked on an evolutionary advantage: the osteoarthritis came along with the knee. However, this painful feature may pay off in the study of human evolution, the researchers stress.

"The idea of tying new features with almost new diseases is a good mental framework to think of while studying these diseases of aging," said Richard. "You can't really have your cake and eat it too."
-end-


Harvard University

Related Osteoarthritis Articles:

App helps reduce osteoarthritis pain
By performing a few simple physical exercises daily, and receiving information about their disease regularly, 500 osteoarthritis patients were able to on average halve their pain in 6 months -- and improve their physical function.
Osteoarthritis can increase your risk for social isolation
In a study published in the Journal of the American Geriatrics Society, researchers examined information from the European Project on OSteoArthritis (EPOSA) study.
High rates of opioid prescriptions for osteoarthritis
Opioids work against severe pain but the risks of side effects and addiction are high.
Disease burden in osteoarthritis is similar to rheumatoid arthritis
Osteoarthritis (OA) has traditionally been viewed as a highly prevalent but milder condition when compared with rheumatoid arthritis (RA), and some may believe that it is part of a normal aging process requiring acceptance, not treatment.
3D printing may help treat osteoarthritis
In a Journal of Orthopaedic Research study, scientists used 3D printing to repair bone in the joints of mini-pigs, an advance that may help to treat osteoarthritis in humans.
Finger joint enlargements may be linked to knee osteoarthritis
Heberden's nodes (HNs) are bony enlargements of the finger joints that are readily detectable in a routine physical exam and are considered hallmarks of osteoarthritis.
Hormone therapy may be best defense against knee osteoarthritis
There is an ongoing debate regarding the relationship between knee osteoarthritis and hormone therapy (HT), with small-scale studies providing mixed results.
Going from negative to positive in the treatment of osteoarthritis
A scientific team has designed a charged molecule that improved the delivery of osteoarthritis drugs to knee joint cartilage in rodent models of the debilitating joint disorder.
Antioxidant defender protects against osteoarthritis
A protein involved in multiple cellular processes called ANP32A protects cartilage in the joints against degradation by damaging oxidation, preventing the development and progression of osteoarthritis, according to a new study by Frederique Cornelis and colleagues.
Symptoms of osteoarthritis lessened with simple changes to the diet
One gram of fish oil a day could help reduce the pain of patients with osteoarthritis, a new study in Rheumatology reports.
More Osteoarthritis News and Osteoarthritis Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.