Cytokine and growth factor expression in Paget's disease: analysis by reverse-transcription/polymerase chain reaction

We investigated expression of several cytokines and growth factors in explants of Pagetic and non-Pagetic bone samples using the technique of reverse-transcription/polymerase chain reaction (RT/PCR). Transcripts for IL-1 alpha and IL-1 beta, TNF-alpha, TNF-beta, IL-6, basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-beta) and insulin-like growth factor-I (IGF-I) were found to a variable degree in both Pagetic and non-Pagetic bone samples, but there was no significant difference in the patterns of expression for these factors in Pagetic bone (n = 18) as compared with non-Pagetic bone (n = 51). There was furthermore, no significant difference in the patterns of expression for the various factors studied when patients were subdivided into mild and severe categories of disease activity using markers of bone formation (serum alkaline phosphatase) or bone resorption (osteoclast counts on adjacent biopsy specimens). Although IL-6 and IL-1 have previously been implicated as bone resorbing factors in Pagetic bone, 40% of our patients with severe disease had not detectable IL-6 transcripts, 70% had no detectable IL-1 alpha transcripts and 50% no IL-1 beta transcripts. We conclude that patterns of expression for cytokine and growth factor mRNAs are not disturbed in Paget's disease. Although we cannot exclude the possibility that post-transcriptional processing of the mRNAs may differ in Pagetic and normal bone cells, our data raise the possibility that the abnormalities of bone turnover which are characteristic of active Paget's disease may be due to local elaboration of other, possibly novel osteotropic factors, which stimulate bone formation and resorption.