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

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.