Evaluation of the role of RANK and OPG genes in Paget's disease of bone

W Wuyts, L Van Wesenbeeck, A Morales-Piga, S Ralston, L Hocking, F Vanhoenacker, R Westhovens, L Verbruggen, D Anderson, A Hughes, W Van Hul

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Abstract

Paget's disease of bone (PDB) is one of the most common bone disorders in the western world. PDB is characterized by focal areas of increased osteoclastic bone resorption and bone formation, which leads to the formation of poorly structured bone. These abnormalities of bone turnover and structure predispose affected individuals to various complications including bone pain, deformity, pathological fracture, and an increased risk of osteosarcoma. One of the main mechanisms of osteoclast formation and activation involves the receptor activator of nuclear factor -kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway, where binding of RANKL to RANK results in the differentiation of osteoclast precursors. OPG, on the other hand, acts as an inhibitor of osteoclastogenesis by serving as a decoy receptor for RANKL. Recently, mutations in the RANK gene have been shown to cause familial expansile osteolysis, a rare bone disorder showing great similarity to PDB. We performed mutation analysis in the RANK and OPG genes in 28 PDB patients to investigate whether mutations in these genes could be responsible for PDB. Our data suggest that RANK is not directly involved in PDB in our set of patients, as no mutations in the RANK coding region could be identified and allele frequencies of RANK polymorphisms did not differ in PDB patients as compared with the random population. Also, in the OPG gene, we could not detect PDB-causing mutations. However, of the several polymorphisms identified, one (400 + 4 C/T in intron 2), showed a statistically significant increased frequency for the C allele in PDB patients, suggesting that individuals harboring this allele may be more susceptible for developing PDB.
Original languageEnglish
Pages (from-to)104-107
Number of pages4
JournalBone
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2001

Keywords

  • carrier proteins
  • DNA mutational analysis
  • DNA primers
  • family health
  • glycoproteins
  • humans
  • membrane glycoproteins
  • molecular sequence data
  • osteitis deformans
  • osteoprotegerin
  • polymorphism, single nucleotide
  • polymorphism, single-stranded conformational
  • RANK ligand
  • receptor activator of nuclear factor-kappa B
  • receptors, cytoplasmic and nuclear
  • receptors, tumor necrosis factor

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    Wuyts, W., Van Wesenbeeck, L., Morales-Piga, A., Ralston, S., Hocking, L., Vanhoenacker, F., Westhovens, R., Verbruggen, L., Anderson, D., Hughes, A., & Van Hul, W. (2001). Evaluation of the role of RANK and OPG genes in Paget's disease of bone. Bone, 28(1), 104-107. https://doi.org/10.1016/S8756-3282(00)00411-7