Protein Interactions May Induce Osteoporosis

The study appeared March 4, 2003, in the online edition of the Journal of Clinical Investigation.

When osteoclast cells reabsorb bone faster than the osteoblast cells are building it, osteoporosis (bone loss) occurs. Previous research had established that M-CSF facilitates the development of unspecialized bone cells into mature osteoclasts. Similarly, it was known that blocking alphaV beta3 integrin in animal models caused failure of osteoclast function.

In the current study, investigators from the Washington University School of Medicine (St. Louis, MO, USA) found that osteoclast precursor cells from a mouse line lacking the beta3 segment grown in tissue culture either failed to develop or were dysfunctional. This behavior contrasted with that seen in living animals, where precursor cells lacking beta3 produced abnormally high numbers of osteoclasts.

"This paradox suggests that something in the living animal interacts with beta3 during the process of osteoclast differentiation,” explained senior author Dr. Steven L. Teitelbaum, professor of pathology and immunology at Washington University Medical School.
When M-CSF was added to the cultured precursor cells, growth defects were reversed. Furthermore, a particular structure on the surface of the cell (c-Fms tyrosine 697, a component of the protein designed to bind to M-CSF) appeared 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,” said Dr. Teitelbaum.



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