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Differentiation of HL-60 Cells into Cells with the Osteoclast Phenotype^*

Division of Endocrinology and Metabolism, Department of Medicine, University of Texas Health Science Center San Antonio, Texas 78284–7877

Address correspondence and requests for reprints to: Dr. Toshiyuki Yoneda, Department of Medicine, Division of Endocrinology and Metabolism, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7877.

Abstract

The osteoclast is the unique multinucleated cell that is responsible for bone degradation in both physiological and pathological circumstances. However, knowledge of the lineage of this inaccessible cell, the nature of its precursors, and the regulation of its formation and activation is limited and controversial. Here we show that the human promyelocytic cell line HL-60 has the potential, under the appropriate culture conditions, to differentiate into cells that have morphological and functional characteristics of osteoclasts, including multinucleation, presence of tartrate-resistant acid phosphatase activity, cross-reactivity with monoclonal antibodies that preferentially recognize osteoclasts, and capacity to resorb bone and respond to calcitonin. The multinucleated cells also contain high affinity receptors to calcitonin, in contrast to wild-type undifferentiated HL-60 cells. These data suggest that osteoclasts share a common precursor with hematopoietic cells. These undifferentiated and differentiated HL-60 cells should provide a unique model for study of the cell biology of human osteoclast differentiation, allowing molecular biological and biochemical studies heretofore not possible.

Footnotes

^* This work was supported by NIH Grants DE-08526 and CA-40035.

Received February 11, 1991.

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