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Receptor activator of NF-B ligand (RANKL) is expressed in chondroblastoma: possible involvement in osteoclastic giant cell recruitment

¹ Department of Orthopaedics and Traumotology, Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR
² Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong
³ Department of Orthopaedic Surgery, University of Western Australia, WA 6009, Australia

Correspondence to:
Professor S M Kumta, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR;
sm-kumta{at}cuhk.edu.hk

Aims: Chondroblastoma is a rare, locally aggressive bone tumour that causes osteolytic destruction at the epiphyseal end of the affected bone. It is possible that tumour cells may stimulate osteoclastogenesis and osteolytic destruction through the production of receptor activator of NF-B ligand (RANKL), which is a key molecule essential for regulating osteoclast formation and activity. Therefore, the expression of RANKL at both the mRNA and the protein level was investigated in chondroblastoma tumour tissue obtained from patients.

Methods: The expression of RANKL gene transcripts was analysed by the reverse transcription-polymerase chain reaction (RT-PCR), and the cellular localisation of RANKL mRNA and protein was demonstrated by means of in situ hybridisation and immunohistochemistry.

Results: RT-PCR analysis indicated that RANKL mRNA was present in all chondroblastoma specimens and normal cancellous bone samples, but not in normal articular cartilage and chondrosarcoma tissues. In contrast, gene transcripts of osteoprotegerin (OPG), the decoy receptor of RANKL, were detected in all types of tissues. The chondroid origin of neoplastic mononuclear cells in chondroblastoma was confirmed by positive S-100 immunohistochemical staining. Both RANKL mRNA and protein were exclusively expressed in these neoplastic mononuclear cells.

Conclusions: These findings suggest that RANKL may be involved in the tumour cell induced recruitment of osteoclast-like cells and consequent osteolytic bone destruction in chondroblastoma.

Keywords: chondroblastoma; receptor activator of NF-B ligand (RANKL); osteoclast-like giant cells

Abbreviations: BSA, bovine serum albumin; DIG, digoxigenin; GCT, giant cell tumour of bone; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Ig, immunoglobulin; IHC, immunohistochemistry; ISH, in situ hybridisation; MMLV, Moloney murine leukaemia virus; OPG, osteoprotegerin; PBS, phosphate buffered saline; RANKL, receptor activator of NF-B ligand; RT-PCR, reverse transcription-polymerase chain reaction; SCC, saline sodium citrate

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