CD44 Antibodies Inhibit Osteoclast Formation

Authors

  • Janice R. Kania,

    1. Department of Pediatrics, Division of Endocrinology and Metabolism, Washington University in St. Louis, St. Louis, Missouri, U.S.A.
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  • Talia Kehat-Stadler,

    1. Department of Pediatrics, Division of Endocrinology and Metabolism, Washington University in St. Louis, St. Louis, Missouri, U.S.A.
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  • Stuart R. Kupfer

    Corresponding author
    1. Department of Pediatrics, Division of Endocrinology and Metabolism, Washington University in St. Louis, St. Louis, Missouri, U.S.A.
    • Stuart R. Kupfer Department of Pediatrics, Box 8116 Division of Endocrinology and Metabolism Washington University in St. Louis St. Louis Children's Hospital, Room 1012 One Children's Place St. Louis, MO 63110 U.S.A.
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Abstract

Osteoclast differentiation is a complex process requiring multiple factors and sequential regulation. We have determined that CD44, a cell surface glycoprotein that is known to function as an adhesion receptor, is involved in this process. By immunocytochemistry, we show that CD44 is expressed in mouse osteoclasts that develop in primary cultures of bone marrow cells treated with 1α,25-dihydroxyvitamin D3. Monoclonal antibodies to CD44 inhibit osteoclast formation in bone marrow cultures in a dose- and time-dependent manner. In contrast, CD44 Fab monomer antibodies have no effect on osteoclast development, suggesting that the inhibition of differentiation by the whole antibodies is facilitated by cross-linking of CD44 molecules. Cocultures of spleen cells and ST2 bone marrow stromal cells indicate that hematopoietic cells mediate the CD44 antibody inhibitory effect. CD44 antibodies do not inhibit osteoclast resorption of calcified matrix, indicating that CD44 is not absolutely required for resorption activity. These observations demonstrate that CD44 may play a role in osteoclast formation and suggest mechanisms by which CD44 antibody effects are mediated.

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