INTEGRINS AND OSTEOCLASTIC RESORPTION IN 3 BONE ORGAN-CULTURES - DIFFERENTIAL SENSITIVITY TO SYNTHETIC ARG-GLY-ASP PEPTIDES DURING OSTEOCLAST FORMATION
G. Vanderpluijm et al., INTEGRINS AND OSTEOCLASTIC RESORPTION IN 3 BONE ORGAN-CULTURES - DIFFERENTIAL SENSITIVITY TO SYNTHETIC ARG-GLY-ASP PEPTIDES DURING OSTEOCLAST FORMATION, Journal of bone and mineral research, 9(7), 1994, pp. 1021-1028
We investigated possible inhibitory effects of five synthetic Arg-Gly-
Asp (RGD)-containing peptides on osteoclastic resorption in three dist
inct in vitro resorption assays (17-day-old fetal mouse bone organ cul
tures) that differ in stages of osteoclast differentiation. RGD peptid
es, which can bind the adhesion receptors called integrins, inhibited
osteoclastic resorption (Ca-45 release) in fetal mouse bone explants i
n which osteoclast precursors have yet to adhere to the mineralized ma
trix and develop into mature osteoclasts (metacarpals and coculture sy
stem). Treatment of metacarpals with RGD peptides inhibited the format
ion of multinucleated TRAP(+) osteoclasts in the mineralized matrix be
cause their mononuclear TRAP(+) osteoclast precursors remained localiz
ed in the periosteum. In particular, echistatin, a viper venom protein
with known affinity for alpha(V) beta(3) integrin, and GdRGDSP inhibi
ted osteoclastic resorption dose dependently in these systems (ED(50)
10(-9) and 10(-4) M, respectively) but did not after the activity of m
ature resorbing osteoclasts in radii. In addition, Ca-45 release was s
ignificantly inhibited by the cyclic peptide GPenGRGDSPCA, which has a
relatively higher affinity for the vitronectin than fibronectin recep
tor(s). In contrast, GRDGdSP, which has a much higher affinity for the
fibronectin receptor (than the vitronectin receptors), had no effect
on resorption at similar concentrations in any resorption system used.
In summary, the data presented in this paper show that peptides with
RGD moths are capable of inhibiting osteoclastic resorption in bone or
gan cultures. Our studies not only support the hypothesis concerning t
he importance of alpha(V) beta(3) in osteoclastic resorption but also
suggest an important role of integrin(s) in events preceding the actua
l resorption of calcified matrix by osteoclasts.