Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis.

Abstract

Pathological osteolyses are considered a consequence of a disturbance in the mechanisms that govern the bone remodeling, mainly the communication between osteoclasts and osteoblasts. Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) are newly discovered molecules that play a key role in these communications. RANKL is essential for osteoclast differentiation via its receptor RANK located on the osteoclast membrane. OPG is a soluble decoy receptor that inhibits osteoclast differentiation through its binding to RANKL. The aim of this study is the analysis of the RANKL/OPG balance by complementary methods (semiquantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay) in human osteolysis associated to various bone etiologies (n = 60), tumoral (primitive, secondary) or not, compared to healthy tissues (n = 16). Results demonstrated that RANKL/OPG ratio was significantly increased in patients suffering from severe osteolysis compared to the control group and that this imbalance is involved in bone resorption mechanisms. In this study, OPG expression appears to reflect a protective mechanism of the skeleton to compensate increased bone resorption by inhibiting osteoclast formation and bone resorbing activity. Moreover, as revealed by immunohistochemistry, RANKL and OPG were colocalized in all of the tissues analyzed. To define the veracity of RANKL/OPG index in assessing and managing patients with severe osteolysis, an extended population of patients suffering from severe osteolysis must be now monitored.

• Authors: Eva Grimaud, Luc Soubigou, Séverine Couillaud, Patrick Coipeau, Anne Moreau, Norbert Passuti, François Gouin, Françoise Redini, Dominique Heymann
• Journal: The American journal of pathology (Am J Pathol) Vol. 163 Issue 5 Pg. 2021-31 (Nov 2003) ISSN: 0002-9440 [Print] United States
• PMID: 14578201 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Carrier Proteins
• Glycoproteins
• Membrane Glycoproteins
• Osteoprotegerin
• RANK Ligand
• RNA, Messenger
• Receptor Activator of Nuclear Factor-kappa B
• Receptors, Cytoplasmic and Nuclear
• Receptors, Tumor Necrosis Factor
• TNFRSF11A protein, human
• TNFRSF11B protein, human
• TNFSF11 protein, human

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Carrier Proteins (genetics, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycoproteins (genetics, metabolism)
• Humans
• Immunohistochemistry
• Male
• Membrane Glycoproteins (genetics, metabolism)
• Middle Aged
• Osteoblasts (metabolism)
• Osteoclasts (metabolism)
• Osteolysis (genetics, metabolism, pathology)
• Osteoprotegerin
• RANK Ligand
• RNA, Messenger (analysis)
• Receptor Activator of Nuclear Factor-kappa B
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Receptors, Tumor Necrosis Factor
• Reverse Transcriptase Polymerase Chain Reaction