OSTEOLYSIS IN BONE LOSS PATHOLOGIES IS ASSOCIATED WITH SIMILAR FACTORS THAT CONTROL OSTEOCLAST FORMATION

Abstract

There is growing evidence that RANKL (also known as osteoclast differentiation factor), its receptor RANK and its natural inhibitor osteoprotegerin (OPG) are involved in bone loss in a number of pathologies. The aim of this study was to determine if these factors are expressed in a number of bone loss pathologies and what cell types were producing these factors in the tissues using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridisation and immunostaining techniques. Periarticular tissue was obtained from 15 patients undergoing revision of aseptic loose implants. Rheumatoid joint tissue was obtained from the pannus region of 12 patients diagnosed with rheumatoid arthritis undergoing joint replacement or joint fusion. Inflamed gingival tissue from sites near bone erosion were obtained from 11 patients with periodontal disease. 6 normal periodontal and periarticular tissue from 6 osteoarthritic patients was used as controls.

RANK, RANKL, OPG and M-CSF mRNA were expressed in tissues obtained from all the pathologies. Higher ratio’s of RANKL to OPG were observed in the pathological tissues compared to their respective controls. In revision tissues many multinucleated giant cell containing particles expressed RANK mRNA. The pattern of staining of RANK mRNA was markedly different in the rheumatoid and periodontal tissues. Differences were also seen in the pattern of expression for RANKL using both in situ and immunostaining. Overall our results indicate that although similar osteoclastogenic factors are fundamentally involved in these bone loss pathologies, different cell types may be producing and/or responding to these factors. Identifying fundamental mechanisms such as these may indicate that similar treatments, such as using OPG or related compounds, may be used for a diverse range of bone loss diseases.