Inhibition of avian osteoclast bone resorption by monoclonal antibody 121F: a mechanism involving the osteoclast free radical system

Collin-Osdoby, Patricia, Li, Li, Rothe, Linda, Anderson, Fred, Kirsch, David, Oursler, Merry Jo and Osdoby, Philip (1998) Inhibition of avian osteoclast bone resorption by monoclonal antibody 121F: a mechanism involving the osteoclast free radical system. Journal of Bone and Mineral Research, 13 1: 67-78. doi:10.1359/jbmr.1998.13.1.67


Author Collin-Osdoby, Patricia
Li, Li
Rothe, Linda
Anderson, Fred
Kirsch, David
Oursler, Merry Jo
Osdoby, Philip
Title Inhibition of avian osteoclast bone resorption by monoclonal antibody 121F: a mechanism involving the osteoclast free radical system
Journal name Journal of Bone and Mineral Research   Check publisher's open access policy
ISSN 0884-0431
1523-4681
Publication date 1998-01
Sub-type Article (original research)
DOI 10.1359/jbmr.1998.13.1.67
Volume 13
Issue 1
Start page 67
End page 78
Total pages 12
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Osteoclast generate high levels of superoxide anions during bone resorption that contribute to the degradative process, although excessive levels of this free radical may be damaging. One mechanism for their removal is via superoxide dismutase (SOD), a protective superoxide scavenging enzyme. We have previously describe a novel developmentally regulated 150 kDa plasma membrane glycoprotein of avian osteoclast which is reactive with the osteoclast-specific monoclonal antibody (Mab) 121F and is related immunological, biochemically, and in protein sequence to mitochondrial Mn2+/Fe2+ SOD. We hypothesized that this unusual osteoclast surface component may be involved in protection against superoxides generated during active bone resorption. Increasing concentrations of monovalent Fab fragments prepared from Mab 121F, but not those another antiosteoclast Mab designated 29C, markedly inhibited both bone particle and bone pit resorption by avian osteoclasts, while reducing tartrate-resistant acid phosphatase activity and causing the morphological contraction of osteoclasts on bone. Thus, the SOD- related membrane antigen may be essential for osteoclast bone resorption. Osteoclast superoxide production, monitored kinetically by cytochrome c reduction and histochemically by nitroblue tetrazolium reduction staining, was significally greater in the presence of 121F, but not 29C, Fab treatment. Furthermore, the release of another free radical known as nitric oxide, which is produced by osteoclasts, can scavenge superoxides, and acts to potently inhibit osteoclast bone resorption, was done-dependently increased by 121F Fab in resorbing osteoclast cultures. Therefore, Mab 121F binding may block the potential protective function of the osteoclast plasma membrane SOD- related glycoprotein, leading to a rapid elevation of superoxide levels and a subsequent rise in osteoclast nitric oxide release, feedback messages which may be sensed by the osteoclast as signals to cease active bone resorption.
Keyword Resistant acid phosphatase
Manganese superoxide dismutase
Nitric oxide synthase
Rat osteoclasts
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article first published online: 1 January 1998.

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Civil Engineering Publications
 
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