Researchers wondering how bone is resorbed have a new toolin a genetically altered mouse whose cultured cells canproliferate continuously, then be coaxed to form mature bone-absorbing osteoclasts for study.

The resulting osteoclasts appear to be 50 to 300 times moreefficient in absorbing bone than previous cell lines. Boneresorbtion is important in osteoporosis, a weakening,progressive condition. Resorbtion occurs naturally duringgrowth as new bone is continually sculpted by sets of cells thatdissolve or secrete bone scaffolding.

The development, by Mark Noble and fellow scientists at St.George's Hospital Medical School and The Ludwig Institute forCancer Research in London, is reported in the current edition ofthe Proceedings of the National Academy of Sciences.

The scientists made transgenic laboratory mice with an"immortalizing" gene from simian virus 40, linked to promoter"switch" from the mouse major histocompatibility complex thatis turned on by gamma interferon.

The immortalizing gene, which allows the mouse cells to growfor untold generations in cell culture, functions in the presenceof gamma interferon at the relatively low body temperature of33 degrees Celsius, but not at a more toasty 39.5 degrees.

Since the precursors of bone-absorbing osteoclasts are rare, thescientists used the mice to establish cultures of bone marrowstromal cells with a "high and sustained" capacity to inducestem cells into becoming mature osteoclasts.

The team also exposed the stem cells to M-CSF (macrophagecolony stimulating factor), supplied by Genetics Institute Inc. ofCambridge, Mass., which predisposes these early-stage bloodcells to become osteoclasts or macrophages.

"Our results suggest that the cell lines we have generatedconsist of precursors that are not yet committed betweenosteoclasts and macrophages," the authors wrote. The scientistsadvise that the undifferentiated cells could be studied to learnwhat unknown signals cause development of the osteoclastitself.

They also concluded that the mouse might be a handy way ofdeveloping cell lines that can produce other rare cell types.

-- Nancy Garcia Associate Editor

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