New hints into development of os...( r cells lacking beta3 produce abnormall...)

"This paradox suggests that something in the living animal interacts with beta3 during the process of osteoclast differentiation," Teitelbaum explains.

His team discovered the interaction may involve M-CSF. When they took precursor cells from mice lacking beta3 and put them in a petri dish very few became osteoclasts. But when levels of M-CSF were increased, the stunted growth effect was reversed. Furthermore, they determined that a particular structure on the surface of the cell (c-Fms tyrosine 697, a component of the protein designed to bind to M-CSF) appears to be largely responsible for this interaction.

"The interaction between M-CSF and alphaV beta3 integrin is intriguing and may help explain some of the less-understood aspects of animal models of osteoporosis," Teitelbaum says.

Because of this interaction, Teitelbaum and colleagues also explored whether alphaV beta3 integrin and M-CSF are involved in the same signaling pathway that causes precursor cells to differentiate into osteoclasts. They found increased levels of M-CSF also restored activity of externally regulated kinases (ERKs) and a protein called c-Fos, which are critical for stimulating the cascade of events that lead to bone-cell differentiation. Since alphaV beta3 integrin also is known to contribute to the activation of ERKs and c-Fos, the team concludes that the alphaV beta3 integrin and M-CSF collaborate in the process of osteoclast differentiation.

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Contact: Gila Z. Reckess
reckessg@msnotes.wustl.edu
314-286-0109
Washington University School of Medicine
4-Mar-2003