CD44 antibodies inhibit osteoclast formation.
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 1 alpha, 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.
Kania
J R
JR
Department of Pediatrics, Washington University, St. Louis, Missouri, USA.
Kehat-Stadler
T
T
Kupfer
S R
SR
D000135:Acid Phosphatase / Q000737:chemistry / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D001862:Bone Resorption / Q000188:drug therapy; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology; D000071681:Tartrate-Resistant Acid Phosphatase
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D008565:Membrane Proteins; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol