Essential for Bones: Osteoprotegerin (OPG, TNFRSF11B)

Mon, 06/23/2014 - 14:28

Also known as OPG, TR1 and OCIF, this gene encodes Osteoprotegerin, a heparin-binding secretory glycoprotein that belongs to the TNF-receptor superfamily. The TNFR superfamily consists primarily of transmembrane proteins that elicit signal transduction in a variety of cells and are known to mediate diverse biological responses, including cytotoxicity and apoptosis, Osteoprotegerin (OPG) was isolated independently by two laboratories in 1997 [1,2]. OPG comprises 401 amino acids of which 21 are a signal peptide which is cleaved and generates the mature form of the protein with 380 amino acids.  OPG is produced as a monomer (55-62 kDa), but undergoes homodimerization and is secreted as a disulphide-linked homodimeric glycoprotein with four or five potential glycosylation sites, generating a mature form of OPG of 110-120 kDa. OPG consists of 7 structural domains of which cysteine rich domainse (D1-D4) are necessary for binding to RANKL, these domains share same features with the extracellular domains of other members of the TNF-receptor family. [3, 4]

The carboxy-terminal portion of OPG contains two putative death domains (D5 and D6). Finally, a heparin-binding site is located in domain 7. The dimeric form of OPG has the highest heparin binding capacity. [3, 4].

One of the unique characteristics of this protein is unlike other receptors of this family, OPG lacks a transmembrane and cytoplasmic domain and as a result is secreted as a soluble protein. [3]

Immunohistochemistry-Paraffin: Osteoprotegerin Antibody Immunohistochemistry-Paraffin: Osteoprotegerin Antibody

OPG is expressed abundantly in many tissues and cell lines and is produced mainly from osteoblasts but besides osteoblasts, OPG is also produced by marrow stromal cells, hematopoietic and immune cells (B cells and dendritic cells), endothelial and vascular smooth muscle cells. [4]

Molecular binding experiments showed OPG associates with RANKL and functions as a decoy receptor and thereby neutralizes its function in osteoclastogenesis. While in vivo studies have shown one of the essential roles of RANK and RANKL is the regulation of bone turnover via osteoclasts and osteoclastogenesis, by contrast mice lacking OPG, show osteoporosis resulting from increased numbers and activities of osteoblasts. The best characterized activity of OPG is the inhibition of osteoclast differentiation and activity, however many other studies strongly support a modulatory role of OPG in hemostasis, vascular injury and inflammation. [5, 6]

As far as the implication in cancer is concerned, OPG serum level has been shown to be elevated in cancer patients, more specifically in patients with more advanced cancer. For instance, OPG levels were increased in the serum of patients with prostate or breast cancer metastatized to bone. [7] Moreover, OPG overexpression has been observed in other types of cancer including epithelial carcinomas of gastroenteric tract. [8] All these investigations suggest that the increased levels of OPG expression could be associated with tumor development and progression. Besides cancer, OPG levels has been shown to be increased in both diabetic and nondiabetic patients affected by coronary artery disease supporting the hypothesis that an abnormal and prolonged elevation of OPG levels, could be an indication of vascular dysfunction. [9]

Novus Biologicals offers Osteoprotegerin reagents for your research needs including:


  1. PMID 9168977
  2. PMID 9108485
  3. PMID 9478964
  4. Atlas Genetics Oncology 
  5. PMID 17363729
  6. PMID 17706953
  7. PMID 12114435
  8. PMID 12838418
  9. PMID 12208791

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