08:53am Tuesday 24 September 2019

UC Davis investigators clarify cellular regulation in the early formation of cartilage and bone

(SACRAMENTO, Calif.) —  A review article by UC Davis Health System investigators details recent research on a family of cell regulators important to the formation and growth of healthy bones and cartilage.

Published in the January 2011 issue of the journal Cartilage, the review gathers for the first time the small but growing body of research to date about these regulators — known as Maf factors — and lays the foundation for understanding the earliest stages of osteoarthritis, a degenerative disease that typically leads to total joint replacement surgery.

“Maf factors may play important roles in cartilage breakdown in early bone development and as people age, when cartilage starts to break down again,” said Dominik Haudenschild, senior author of the review and a UC Davis Health System assistant professor of orthopaedic surgery. “The more we learn about the genetic regulators that are active during the breakdown process, the more we can understand how to treat osteoarthritis before surgery is necessary.”

Osteoarthritis occurs from the breakdown and eventual loss of cartilage that normally serves as a cushion between bones at joints. Pain occurs as the bones rub together, most often in the hips and knees. Although it can be treated with pain-relief and anti-inflammatory medications, there is no cure. Surgery is currently the most effective way to restore mobility and reduce discomfort.

In the review, Haudenschild describes how a cartilage model of the future skeleton is formed during fetal development. As development continues, the cartilage dissolves and is replaced by bone, with cartilage remaining mainly in joints. The complicated process is regulated by genetic transcription factors, which control the various enzymes and proteins needed to carry out the steps.

Until recently, research on chondrocytes — the cells that form cartilage — has focused on the “sox” and “runx” families of genetic regulators, which are known to be important for cartilage and bone development. Sox9 is known as the “master regulatory gene” for cartilage, while runx regulators are important as chondrocytes turn into bone.

Less well understood is the Maf family. The review describes how these regulators are expressed in chondrocytes during late growth at the ends of bones in embryonic cartilage models. Interestingly, Maf-active chondrocytes behave similarly to chondrocytes in cartilage that is disintegrating due to the progression of osteoarthritis.

Haudenschild leads an active research laboratory at UC Davis that specializes in identifying molecular signals that promote cartilage stability and prevent its degeneration, with the specific goal of finding new and less-invasive treatments for osteoarthritis. In doing so, his multidisciplinary team combines the fields of molecular and cell biology, tissue and biomedical engineering, and biochemistry. This team is currently conducting experiments to confirm the relationship between Maf factors and osteoarthritis by identifying genetic targets in cartilage controlled by these factors.

“Joint replacement is one of the most commonly performed surgeries in the country,” said Haudenschild. “Our comprehensive approach to understanding the cellular processes that prevent osteoarthritis can lead to non-surgical therapies that can stop or slow that disease process or even enhance cartilage growth.”

Additional UC Davis Department of Orthopaedic Surgery authors of “Role of c-Maf in Chondrocyte Differentiation: A Review” included Eunmee Hong, post-doctoral research fellow and lead author, and Paul E. DiCesare, professor and chair.

The UC Davis Department of Orthopaedic Surgery provides comprehensive medical and surgical care of the musculoskeletal system for both adults and children. As a leading West Coast center for orthopaedic care and a leading partner in the world-renowned UC Davis Trauma Center, the department provides a full spectrum of treatment specialties, including joint reconstruction, microvascular surgery, sports medicine and pediatric orthopaedics. The department was ranked 35th nationally for 2010-2011 among orthopaedic surgery departments nationwide by U.S. News & World Report. For more information, visit the department’s website.

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