Retinoic acid stimulates expression of the functional osteoclast integrin alpha v beta 3: transcriptional activation of the beta 3 but not the alpha v gene

J Cell Biochem. 1996 Sep 15;62(4):467-75. doi: 10.1002/(SICI)1097-4644(19960915)62:4%3C467::AID-JCB4%3E3.0.CO;2-K.

Abstract

The capacity of osteoclasts to resorb bone depends, in part, on the surface expression of the integrin alpha v beta 3. We have investigated whether the steroid hormone retinoic acid, known to stimulate bone resorption, regulates the appearance of the alpha v beta 3 complex in avian osteoclast presursors. Using surface labeling, followed by immunoprecipitation with a alpha v beta 3-specific antibody, we show that retinoic acid increases surface expression of the heterodimer in a dose- and time-dependent manner. Northern analysis reveals that the high basal steady-state levels of alpha v mRNA do not change, while those for beta 3 rise significantly from their initially low levels. Nuclear run-on studies confirm that steroid treatment stimulates transcription of the beta 3, but not the alpha v gene. Osteoclast precursors treated with retinoic acid exhibit increased multinucleation and expression of the osteoclast marker enzyme tartrate-resistant acid phosphatase. However, the fused cells do not have an increased capacity to resorb bone. In summary, multinucleated cells generated in this study do not represent fully differentiated bone-resorbing polykaryons. These results suggest that treatment of osteoclast precursors with retinoic acid is necessary, but insufficient, for expression of the mature osteoclast phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Bacterial Proteins*
  • Calcitriol / pharmacology
  • Chick Embryo
  • Integrin beta3
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Platelet Membrane Glycoproteins / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Receptors, Vitronectin / biosynthesis*
  • Receptors, Vitronectin / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects*
  • Tretinoin / pharmacology*

Substances

  • Antigens, CD
  • Bacterial Proteins
  • Integrin beta3
  • MtrB protein, Bacteria
  • Platelet Membrane Glycoproteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Vitronectin
  • Transcription Factors
  • Tretinoin
  • Calcitriol