Characterization of monomeric and homodimeric forms of osteoclastogenesis inhibitory factor.
Abstract
Osteoclastogenesis inhibitory factor (OCIF) is present naturally as two molecular forms, a monomer and a homodimer. The two forms of recombinant human OCIF (rOCIF) produced by Chinese hamster ovary (CHO) cells were purified to homogeneity. Determination of the C-terminal amino-acid sequences of the two forms of rOCIF revealed that the monomeric rOCIF lacked several amino acids including Cys379, which is involved in the intermolecular disulfide bond, in its C-terminal region. The two forms of rOCIF were indistinguishable in stability, sialic acid content, and specific activity in inhibition of osteoclastogenesis. In contrast, the homodimeric rOCIF was stronger in heparin-binding ability than the monomeric rOCIF. The homodimeric rOCIF was significantly shorter in initial half-life and smaller in AUC value in rats than the monomeric rOCIF, but exerted more potent biological activity in reducing the calcium concentration in serum of rats than did the monomeric rOCIF.
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Heparin binding by native OPG likely limits its distribution and half-life, so serum OPG may have limited ability to influence osteoclasts within bone.
“Heparin binding by native OPG is likely to limit its distribution and half-life ( 18) such that OPG measured in serum might have limited potential to influence osteoclasts within bone.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [18]
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- Authors
- Tomoyasu, A., Goto, M., Fujise, N., Mochizuki, S.-I., Yasuda, H., Morinaga, T., Tsuda, E., & Higashio, K.
- Affiliations
- Megmilk Snow Brand (Japan) (JP)
- Corresponding author
- Goto, Masaaki
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1998-04
- Volume
- 245
- Issue
- 2
- Pages
- 382-387
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2133418994
- Cited by
- 83
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 2 · 2012: 2
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- osteoprotegerin, homodimer, monomers, recombinant protein, C-terminal sequence, disulfide bonds, sialic acid, heparin binding, protein stability, serum calcium, osteoclastogenesis inhibition, pharmacokinetics
- MeSH terms
- Amino Acid Sequence, Animals, Calcium, Disulfides, Glycoproteins, Cricetinae, Heparin, Humans, Molecular Sequence Data, Protein Binding, Recombinant Proteins, CHO Cells, Sequence Analysis, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, N-Acetylneuraminic Acid, Dimerization, Osteoprotegerin
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