Cytokines Expressed in Multinucleated Cells: Paget's Disease and Giant Cell Tumors versus Normal Bone |
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Authors: | B G Mills A Frausto |
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Institution: | (1) University of Southern California Schools of Dentistry and Medicine, Los Angeles, California, USA, US;(2) J. Vernon Luck Research Center, Orthopaedic Hospital, 2400 South Flower Street, Los Angeles, California 90007-2629, USA, US |
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Abstract: | Human osteoclasts are well characterized multinucleated cells whose function is the directed resorption of normal bone (NB).
Osteoclastic bone destruction accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of bone and giant
cell tumors of bone (GCTB). The mechanism of this stimulation of osteoclastic bone resorption is unknown. This study was designed
to detect cytokines present in the multinucleated cells of PD and GCTB in order to determine whether cytokine abnormalities
exist to account for bone lysis. Nine cytokines, representing the functions of bone resorption, angiogenesis, tumor necrosis,
bone cell proliferation, and osteoblast–osteoclast coupling, were examined by immunohistochemistry using tissue samples from
15 NB, 17 PD, and 19 GCTB patients. Standard nonparametric statistical analysis showed a significant increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB for interleukin-6 (Il-6), tumor necrosis factor beta (TNFβ),
epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). There was
a statistically significant decrease in immunostaining of giant cells of GCTB as compared with NB for transforming growth
factor beta (TGFβ), but no other differences from normal osteoclasts. The increase in staining of PD osteoclasts over the
giant cells of GCTB was significant (P < 0.01) for Il-6, TNFβ, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P < 0.05) for Il-1 and EGF. It was concluded that marked cytokine differences exist in vivo between osteoclasts of NB and PD lesions consistent with stimulated resorption. Alternatively, ``osteoclastoma' cells in
the center of the tumor did not overexpress the cytokines associated with bone lysis, suggesting some other mechanism for
stimulated resorption.
Received: 12 February 1996 / Accepted 31 December 1996 |
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Keywords: | : Cytokines — Osteoclasts — Paget's disease — Osteoclastoma |
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