RRC ID |
39339
|
著者 |
Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, Ikeda K, Higashio K, Yamada Y.
|
タイトル |
Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis.
|
ジャーナル |
J Bone Miner Res
|
Abstract |
Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family of proteins and plays an important role in the negative regulation of osteoclastic bone resorption. Whether OPG/OCIF circulates in human blood and how its level changes under pathological conditions is not known. To address these issues, a panel of monoclonal antibodies was generated against recombinant OPG/OCIF and screened for reactivity with solid-phase monomeric and homodimeric forms of the recombinant protein. Antibodies that showed high affinity for both forms of OPG/OCIF and those that selectively recognized the homodimer were identified, enabling development of two types of sensitive enzyme-linked immunosorbent assay (ELISA): one that detects both forms of OPG/OCIF equally and one specific for the homodimer. Characterization of circulating OPG/OCIF with these ELISAs revealed that the protein exists in human serum mainly in the monomeric form. The serum concentration of OPG/OCIF increased with age in both healthy Japanese men and women, and was significantly higher in postmenopausal women with osteoporosis than in age-matched controls. Within the osteoporotic group, serum OPG/OCIF concentrations were higher in patients with low bone mass. Serum OPG/OCIF concentrations were also significantly increased in those postmenopausal women with a high rate of bone turnover, as determined by increased serum bone-specific alkaline phosphatase and urinary excretion of pyridinoline and deoxypyridinoline. The results suggested that circulating OPG/OCIF levels are regulated by an age-related factor(s) and that the increased serum concentration may reflect a compensative response to enhanced osteoclastic bone resorption and the resultant bone loss rather than a cause of osteoporosis.
|
巻・号 |
14(4)
|
ページ |
518-27
|
公開日 |
1999-4-1
|
DOI |
10.1359/jbmr.1999.14.4.518
|
PMID |
10234572
|
MeSH |
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Monoclonal
Antibody Specificity
Bone Density
Bone Diseases, Metabolic / blood
Bone Diseases, Metabolic / metabolism
Case-Control Studies
Dimerization
Enzyme-Linked Immunosorbent Assay
Female
Glycoproteins / blood*
Glycoproteins / chemistry
Glycoproteins / immunology
Humans
Male
Mice
Middle Aged
Osteoporosis, Postmenopausal / blood*
Osteoporosis, Postmenopausal / metabolism
Osteoprotegerin
Protein Conformation
Receptors, Cytoplasmic and Nuclear*
Receptors, Tumor Necrosis Factor
Recombinant Proteins / chemistry
Recombinant Proteins / immunology
|
IF |
5.854
|
引用数 |
324
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
リソース情報 |
ヒト・動物細胞 |
ST2(RCB0224) |