Nav: Home

How the heart turns into bone

November 17, 2016

Connective tissue cells in the heart turn into bone-producing cells in response to injury, University of California, Los Angeles scientists report November 17 in Cell Stem Cell. The discovery helps explain why some people who survive heart damage develop abnormal calcium deposits--the main component of bone--in the valves or walls of the heart. The researchers also show that heart calcification can be prevented in mice by blocking an enzyme that regulates bone mineralization with small molecules.

Tissues outside of the bones don't naturally calcify, yet mineralization of organs, including the heart, blood vessels, and kidneys, occurs with age and is exacerbated in people with diabetes or kidney disease. In the heart, calcification can disrupt electrical conduction and lead to heart blocks. Once the calcium deposits form in tissues, there are currently no treatments to break them down.

"Heart calcification has been understudied and underreported," says senior author Arjun Deb, of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research based at the University of California, Los Angeles. "We asked the question, 'What are the cells in the heart that cause calcification?' and given the strong association between tissue injury, fibrosis, and calcification, we hypothesized that maybe it is cardiac fibroblasts [cells that give rise to scar tissue after injury] that are contributing to the calcification process."

To find out, Deb and his co-authors genetically tagged cardiac fibroblasts in mice and watched as they transitioned into bone-forming, osteoblast-like cells after heart injury. The researchers transplanted the cardiac fibroblasts isolated from the region of calcification under the skin of healthy mice and observed soft-tissue calcification similar to that seen in the donor mice. Human cardiac fibroblasts were also observed to be capable of forming similar calcium deposits in a laboratory dish.

Deb and his team then asked whether heart calcification could be prevented or treated using small molecules. Their best lead for a drug target was a protein called ENPP1 that seemed to be overexpressed by the heart, and specifically by cardiac fibroblasts, in response to injury. The researchers injected several different small molecules that could disrupt the activity of ENPP1 and observed a decrease of 50% or more in the extent of calcium deposition. Injection of a drug called etidronate led to a 100% rescue with no calcification after injury.

"We now want to see whether this is a common pathway to calcification regardless of etiology and if what we found can be broadly applied to tissues across the body," says Deb, who also holds several posts at the UCLA David Geffen School of Medicine.

His research group has already begun looking in patient cells to see whether blood vessel calcification can be prevented using the small molecule approach. They also want to explore potential drugs that could render calcification reversible, as the ENPP1 approach only worked to prevent calcium deposits when injected in advance of injury.
-end-
This work was primarily supported by the National Institutes of Health, the California Institute of Regenerative Medicine, the Department of Defense, the Oppenheimer Foundation, and a James Eason Cardiovascular Discovery Award.

Cell Stem Cell, Pillai and Li et al.: "Cardiac fibroblasts adopt osteogenic fates and can be targeted to attenuate pathological heart calcification" http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)30345-9

Cell Stem Cell (@CellStemCell), published by Cell Press, is a monthly journal that publishes research reports describing novel results of unusual significance in all areas of stem cell research. Each issue also contains a wide variety of review and analysis articles covering topics relevant to stem cell research ranging from basic biological advances to ethical, policy, and funding issues. Visit: http://www.cell.com/cell-stem-cell. To receive Cell Press media alerts, contact press@cell.com.

Cell Press

Related Injury Articles:

Microbleeds may worsen outcome after head injury
Using advanced imaging, researchers have uncovered new information regarding traumatic microbleeds, which appear as small, dark lesions on MRI scans after head injury but are typically too small to be detected on CT scans.
Which car crashes cause traumatic brain injury?
Motor vehicle crashes are one of the most common causes of TBI-related emergency room visits, hospitalizations and deaths.
From spinal cord injury to recovery
Spinal cord injury disconnects communication between the brain and the spinal cord, disrupting control over part of the body.
Can a nerve injury trigger ALS?
Researchers at the University of Illinois at Chicago are the first to demonstrate that a peripheral nerve injury can trigger the onset and spread of the disease in an animal model of ALS.
A new approach to peripheral nerve injury?
The lab of neuroscientist Michael Costigan, Ph.D., at Boston Children's Hospital is studying how the body's immune system breaks down damaged peripheral nerves.
More Injury News and Injury Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...