UAB Researcher Probes Role of a Master Gene in Skeletal Formation

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Newswise BIRMINGHAM, Ala. Amjad Javed, Ph.D., of the University of Alabama at Birmingham, has taken a major step forward in understanding the bone development function of a gene called runx2, which could lead to future ways to speed bone healing, aid bone bioengineering, stem osteoporosis and reduce arthritis.

Javed, a professor in the UAB School of Dentistrys Department of Oral and Maxillofacial Surgery, says the results will contribute to future personalized medicine. This month, Javed presented this work to a standing-room-only audience at the International Association for Dental Research Annual Meeting in Boston. The work was published recently in two articles in the Journal of Bone and Mineral Research.

It was well-known that the deletion of both copies of the runx2 gene is lethal and the organism cannot form bone, teeth or cartilage.

To learn about the function of runx2 in specific cells types, Javed and his colleagues developed mice in which both copies of the runx2 gene were removed in only one of two key cells for bone tissue either chondrocytes or osteoblasts.

Our objective was to dissect and tease out which cell is really contributing what in bone development, Javed said. Runx2 is vital. But when we talk up personalized medicine, we need to identify which specialized cells to target within bone tissue.

Study of these mice (technically known as the next-generation conditional knockout runx2 model) shows that chondrocytes and osteoblasts have surprisingly different functions in bone formation during gestation or after birth:

Chondrocytes are involved in bone mineralization during embryonic development. Osteoblasts are involved in bone growth during postnatal development. This is a major step forward in understanding the biology of bones the dynamic, complex organs that are actively remodeled throughout life. Bones have cartilage-producing cells (chondrocytes), bone-creating cells (osteoblasts), bone-eating cells (osteoclasts), neuronal cells and blood-forming (hematopoietic) cells. Connective tissue and muscle surround the bones.

Chondrocytes Javeds model began with the cartilage-producing cells. We first removed the runx2 gene in chondrocytes, cells that are fundamental for every cartilage tissue in the body, Javed said. Our first surprise was lethality at birth.

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UAB Researcher Probes Role of a Master Gene in Skeletal Formation