A Glanzmann's mutation in beta 3 integrin specifically impairs osteoclast function.

Academic Article


  • Osteoclastic bone resorption requires cell-matrix contact, an event mediated by the alpha v beta 3 integrin. The structural components of the integrin that mediate osteoclast function are, however, not in hand. To address this issue, we generated mice lacking the beta 3 integrin gene, which have dysfunctional osteoclasts. Here, we show the full rescue of beta 3(-/-) osteoclast function following expression of a full-length beta 3 integrin. In contrast, truncated beta 3, lacking a cytoplasmic domain (h beta 3c), is completely ineffective in restoring function to beta 3(-/-) osteoclasts. To identify the components of the beta 3 cytoplasmic domain regulating osteoclast function, we generated six point mutants known, in other circumstances, to mediate beta integrin signaling. Of the six, only the S(752)P substitution, which also characterizes a form of the human bleeding disorder Glanzmann's thrombasthenia, fails to rescue beta 3(-/-) osteoclasts or restore ligand-activated signaling in the form of c-src activation. Interestingly, the double mutation Y(747)F/Y(759)F, which disrupts platelet function, does not affect the osteoclast. Thus similarities and distinctions exist in the mechanisms by which the beta 3 integrin regulates platelets and osteoclasts.
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    Published In


  • Amino Acid Sequence, Animals, Antigens, CD, Bone Resorption, Cell Size, Cytoskeleton, Integrin beta3, Integrins, Mice, Mice, Knockout, Molecular Sequence Data, Osteoclasts, Platelet Membrane Glycoproteins, Point Mutation, Protein Structure, Tertiary, Proto-Oncogene Proteins pp60(c-src), Sequence Homology, Amino Acid, Stem Cells, Thrombasthenia
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    Author List

  • Feng X; Novack DV; Faccio R; Ory DS; Aya K; Boyer MI; McHugh KP; Ross FP; Teitelbaum SL
  • Start Page

  • 1137
  • End Page

  • 1144
  • Volume

  • 107
  • Issue

  • 9