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Cell. 1997 Jun 27;89(7):1021-31.

Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses osteopetrosis in op/op mice.

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Department of Pathology, Stanford University School of Medicine, California 94305, USA.


Osteopetrotic (op/op) mice lack functional M-CSF and have depressed levels of macrophages and osteoclasts. We prepared transgenic mice (hMRP8bcl-2) that express human Bcl-2 in monocytes. In vitro hMRP8bcl-2 monocytes do not undergo apoptosis in the absence of serum and M-CSF, while op/op and wild-type monocytes die. These Bcl-2-expressing monocytes spontaneously undergo macrophage differentiation. In vivo, the op/op hMRP8bcl-2 mice show significant replenishment of tissue macrophages. Their long bone osteopetrosis is largely reversed, and extensive medullary hematopoiesis appears in the bone marrow. We propose that M-CSF augments monocyte survival, permitting them to respond to internal and external cues for their differentiation.

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