UCSF Researchers Convert Fat Cells to Bone Cells

October 14, 2002
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UCSF scientists used a vitamin A derivative, retinoic acid, to inhibit fat conversion and in concert with a substance known to promote bone growth --- so-called bone morphogenic protein (BMP) --- converted pre-fat type cells into true bone cells that deposit bone matrix.

Rik Derynck, UCSF professor in the School of Dentistry's department of growth and development, said, "We used preadipocytes, which are pre-fat cells and explored whether treatments directed from outside the cell itself could redirect their fate from future fat cells to future bone cells."

Derynck, who is the director of the new UCSF Center for Craniofacial and Mesenchymal Biology, said for a cell to convert from one cell type to another, there must be suppression of the original cell type with promotion of differentiation to the new type.

The scientists found that the particular pre-fat cells used -- a cell line known as 3T3-F442A cells -- had special receptors as well as specific genes known to be involved in signal transduction, called Smads, that are needed for BMP to work. A particular BMP -- BMP-2 -- increased proliferation of the cells, and caused a very mild effect suggesting that these cells could be converted into bone cells. However, it was only after the researchers combined BMP with retinoic acid that the cells were no longer able to develop into fat cells and, instead, converted into mature bone cells.

The new bone cells have all the hallmarks associated with bone formation, including production of bone proteins like osteocalcin and calcification or mineralization, as happens whenever true bone forms, Derynck said. Further, this happened at the expense of fat formation that would have occurred without the induction of special additives.

The researchers believe that under the right conditions, retinoids could cooperate with BMP to redirect pre-fat cells into true bone cells, provided the levels of BMP receptors are sufficiently high. Derynck said, "With the use of these two signaling systems, one can do things that one has not thought of before. In effect, the life of these fat cells has been changed from fat to bone. Now we can begin to think about therapeutic applications.

In addition, the study results indicate that other related substances can exert similar effects in fat and bone formation by these cells. The UCSF scientists plan future studies to characterize the molecular mechanisms of the cooperation of retinoic acid with BMP.

The results of the study will be published in the October 14 issue of The Journal of Cell Biology. The study was funded by grants from the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the Arthritis Foundation, and a fellowship from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Co-authors on the study are Jeremy Skillington, PhD, UCSF postdoctoral fellow, and Lisa Choy, PhD, UCSF assistant adjunct professor.

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