A HUMAN HOMOLOG OF THE 150 KD AVIAN OSTEOCLAST MEMBRANE ANTIGEN-RELATED TO SUPEROXIDE-DISMUTASE AND ESSENTIAL FOR BONE-RESORPTION IS INDUCED BY DEVELOPMENTAL AGENTS AND OPPOSED BY ESTROGEN IN FLG-29.1 CELLS
Z. Khalkhaliellis et al., A HUMAN HOMOLOG OF THE 150 KD AVIAN OSTEOCLAST MEMBRANE ANTIGEN-RELATED TO SUPEROXIDE-DISMUTASE AND ESSENTIAL FOR BONE-RESORPTION IS INDUCED BY DEVELOPMENTAL AGENTS AND OPPOSED BY ESTROGEN IN FLG-29.1 CELLS, Calcified tissue international, 60(2), 1997, pp. 187-193
Osteoclast development from hematopoietic bone marrow precursors is as
sociated with the expression of various enzymes, receptors, adhesion m
olecules, and other specialized components. Among these is a novel 150
kD superoxide dismutase-related membrane glycoprotein, originally ide
ntified by its reaction with the anti-osteoclast monoclonal antibody 1
21F. This antigen is uniquely restricted to osteoclasts in bone, unive
rsally present on osteoclasts from multiple species, induced during os
teoclast differentiation in vitro and in ovo, and required at high lev
els for avian osteoclastic bone pit resorption. Expression of a compar
able human antigen was investigated using human leukemic FLG 29.1 cell
s capable of differentiating towards an osteoclast-like phenotype. Pho
rbol ester, 1,25 (OH)(2) vitamin D-3, and osteoblast-derived soluble f
actors elicited dose and time-dependent inductions of this antigen as
measured by enzyme-linked immunosorbent assay (ELISA) and immunocytoch
emical staining, coincident with their display of multiple other osteo
clastic features. Synergistic interactions of these modulators led to
further elevations in the ultimate expression levels of this antigen,
although not to the full extent associated with in vivo-formed avian o
steoclasts. The potent antiresorptive hormone 17 beta-estradiol, but n
ot its inactive alpha isomer, partially suppressed the phorbol ester-i
nduced elevation of the 121F antibody-reactive antigen in FLG 29.1 cel
ls as it does in avian osteoclast-like cells. Characterization of the
human antigen isolated from FLG 29.1 cells by 121F immunoaffinity puri
fication demonstrated that this regulated membrane component was synth
esized by these human cells, more abundant following their differentia
tion into osteoclast-like cells, and similar biochemically and immunol
ogically to the 150 kD integral membrane glycoprotein previously descr
ibed from avian osteoclasts. Therefore, this report is the first docum
entation that human osteoclast-like FLG 29.1 cells express, in a devel
opmentally regulated fashion, a homolog of the specific 150 kD avian o
steoclast surface antigen that is related to superoxide dismutase, a p
rotective free radical scavenging enzyme and is essential for osteocla
stic bone resorption.