Osteoarthritic stem cell discovery hints at disease’s first drug treatments

DISCOVERY: Life­span researchers Chathuraka T. Jayasuriya, left, and Qian Chen, both of Rhode Island Hospital and the Warren Alpert Medical School of Brown University, have discovered aberrant stem cells that may play a role in osteoarthritis. / PBN PHOTO/
MICHAEL SALERNO
DISCOVERY: Life­span researchers Chathuraka T. Jayasuriya, left, and Qian Chen, both of Rhode Island Hospital and the Warren Alpert Medical School of Brown University, have discovered aberrant stem cells that may play a role in osteoarthritis. / PBN PHOTO/
MICHAEL SALERNO

A May report by a team of researchers from Rhode Island Hospital and Brown University shows that a portion of unspecialized stem cells in joint cartilage of osteoarthritis patients may be advancing the disease. The finding could lead to the development of the first drug treatments for osteoarthritis.

Until recently, medical wisdom held that cartilage consisted only of cartilage-making cells, chondrocytes. In 2004, researchers discovered cartilage-derived mesenchymal stem cells in bovine cartilage, said Chathuraka T. Jayasuriya, assistant professor of orthopaedics at Rhode Island Hospital and assistant professor of orthopaedics at the Warren Alpert Medical School of Brown University, lead author on the study.

Osteoarthritis, sometimes called degenerative joint disease or “wear and tear” arthritis, damages the cartilage covering the ends of bones, which normally allow smooth movement in the joint. The disease causes pain, stiffness and swelling, most frequently in the hands, hips and knees. The bone itself can break down as the disease progresses. Pain management and eventual joint replacement are the only available treatments, but that might be about to change.

Co-author Qian Chen, chair in orthopaedic research at the Warren Alpert Medical School of Brown University and director of the Center of Biomedical Research Excellence in Skeletal Health and Repair at Rhode Island Hospital, said there are two forms of the disease: primary, caused by aging; and secondary, seen in younger people, caused by injury.

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Chen said they’ve found mesenchymal stem cells in osteoarthritic cartilage that play a role in primary osteoarthritis. Osteoarthritic mesenchymal stem cells make up 1 percent or less of normal cartilage and 10 percent of osteoarthritis cartilage in people, Chen said.

When a joint suffers an injury, the mesenchymal stem cells become active to help repair the damage, Chen said. However, the stem cells age along with the person, hampering their regenerative ability.

The newly discovered stem cells’ numbers increase as patients age and osteoarthritis progresses, expressing tissue-degrading enzymes and possibly promoting the mineralization of cartilage, according to the study, “Molecular characterization of mesenchymal stem cells in human osteoarthritis cartilage reveals contribution to the OA phenotype,” in the journal Scientific Reports.

The study, said Jayasuriya, was supported by two research grants held by the hospital and the university – a $5.8 million grant from the Center of Biomedical Research Excellence in Skeletal Health and Repair running through 2022 and a $75,000 pilot project grant from Advance Clinical Translational Research to pay the direct cost for research, both funded by the National Institute of General Medicine.

“People always think that stem cells are good for repair,” Chen said, but their research shows that’s not necessarily the case with osteoarthritic mesenchymal stem cells.

‘We may be able to target the stem cells, eliminating them or preventing … proliferation.’
CHATHURAKA T. JAYASURIYA, Rhode Island Hospital assistant professor of orthopaedics

Even so, the discovery points toward possible therapies for primary osteoarthritis that affect the aging stem cells, said Jayasuriya.

“These stem cells are a precursor to the chondrocytes that we’ve long associated with osteoarthritis. We may be able to target the stem cells, eliminating them or preventing their proliferation, and saving valuable cartilage for a longer period of time,” he said.

That development would be a boon for many older people. Osteoarthritis is the most common form of disability in American adults, and the fifth-most prevalent disability worldwide, according to the Arthritis Foundation. Osteoarthritis was the highest cause of work loss and affected more than 20 million individuals in 2012, costing the U.S. economy more than $100 billion annually, according to the foundation.

The disease affects more than 30 million Americans, according to the Centers for Disease Control and Prevention. In Rhode Island, about one-third of the older population has osteoarthritis, Chen said.

There are no Food and Drug Administration-approved drugs for osteoarthritis, Chen said, so the discovery of cells that contribute to the disease points the way toward finding such medicines. “We think in the future, there could be drugs developed for joint repair,” he said.

Healthy cartilage-derived mesenchymal stem cells could also be isolated and grown in a lab to be used in tissue generation for cartilage repair.

“I would expect in a couple years there could be clinical trials” for such drugs, said Chen. He and Jayasuriya agreed the discovery could lead to treatments within 10 years.

The other authors on the osteoarthritis study were Dr. Richard Terek, Dr. Michael G. Ehrlich and Nicholas Lemme of Rhode Island Hospital and Brown University, and Nan Hu and Jing Li of Xi’an Jiaotong University in Xi’an, China.