TY - JOUR
T1 - Activation of α(v)β3 integrin on human osteoclast-like cells stimulates adhesion and migration in response to osteopontin
AU - Faccio, R.
AU - Grano, M.
AU - Colucci, S.
AU - Zallone, A. Zambonin
AU - Quaranta, V.
AU - Pelletier, A. J.
N1 - Funding Information:
This work was supported by NIH awards #GM53489 awarded to AJP, DE10063 awarded to VQ and awards from A.I.R.C. (The Italian Association for Cancer Research), A.S.I. (The Italian Space Agency) and M.U.R.S.T. to AZZ.
PY - 1998/8/19
Y1 - 1998/8/19
N2 - Integrins mediate cell adhesion and can induce different cellular responses, including changes in intracellular pH, changes and oscillation in intracellular free calcium, and protein phosphorylation on tyrosine. During bone resorption, the integrin α(v)β3 regulates adhesion of osteoclasts to bone extracellular matrix proteins, such us osteopontin (Opn). Adhesion via α(v)β3 is followed by osteoclast polarization onto the bone surface and by the onset of bone resorption. To characterize these events at the molecular level, we investigated the state of activation of α(v)β3 on the human osteoclast-like cell line GCT23 using the monoclonal antibody AP5 which binds to and can induce, under low calcium conditions, activated α(v)β3. By flow cytometry, approximately 50% of α(v)β3 on the surface of the osteoclast-like cell line GCT23 was reactive with AP5 and was therefore in the activated state. Incubation with AP5 in the presence of low calcium concentrations increased activated α(v)β3 to 90-100%. Activation of α(v)β3 increased the efficiency of GCT23 adhesion to Opn by 2-fold. Furthermore, haptotactic migration on Opn was also enhanced about 40% compared to control. We propose that changes in the activation state of α(v)β3 may be a regulation point for osteoclasts during bone resorption.
AB - Integrins mediate cell adhesion and can induce different cellular responses, including changes in intracellular pH, changes and oscillation in intracellular free calcium, and protein phosphorylation on tyrosine. During bone resorption, the integrin α(v)β3 regulates adhesion of osteoclasts to bone extracellular matrix proteins, such us osteopontin (Opn). Adhesion via α(v)β3 is followed by osteoclast polarization onto the bone surface and by the onset of bone resorption. To characterize these events at the molecular level, we investigated the state of activation of α(v)β3 on the human osteoclast-like cell line GCT23 using the monoclonal antibody AP5 which binds to and can induce, under low calcium conditions, activated α(v)β3. By flow cytometry, approximately 50% of α(v)β3 on the surface of the osteoclast-like cell line GCT23 was reactive with AP5 and was therefore in the activated state. Incubation with AP5 in the presence of low calcium concentrations increased activated α(v)β3 to 90-100%. Activation of α(v)β3 increased the efficiency of GCT23 adhesion to Opn by 2-fold. Furthermore, haptotactic migration on Opn was also enhanced about 40% compared to control. We propose that changes in the activation state of α(v)β3 may be a regulation point for osteoclasts during bone resorption.
UR - http://www.scopus.com/inward/record.url?scp=0032547155&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1998.9180
DO - 10.1006/bbrc.1998.9180
M3 - Article
C2 - 9712729
AN - SCOPUS:0032547155
SN - 0006-291X
VL - 249
SP - 522
EP - 525
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -