OSTEOCLASTS IN NORMAL AND ADJUVANT ARTHRITIS BONE TISSUES EXPRESS THEMESSENGER-RNA FOR BOTH TYPE-I AND TYPE-II INTERLEUKIN-1 RECEPTORS

Osteoclasts are known to play a crucial role in both physiologic and p athologic bone resorption. Moreover, it is generally agreed that IL-1 has powerful effects on osteoclastic bone resorption, although the pre cise cellular sites and mechanisms by which IL-1 mediates osteoclastic bone resorption remain unclear. In particular, it is still controvers ial whether osteoclasts can respond to IL-1 directly. The expression o f mRNA for type I IL-1 receptor (IL-1RI) and type II IL-1 receptor (IL -1RII) in osteoclasts was investigated in normal and inflammatory bone tissues by in situ hybridization to determine whether osteoclasts are the target cells for IL-1 and to elucidate the mechanism by which IL- 1 induces osteoclastic bone resorption. For this study, normal tibiae were obtained from newborn, young, and adult mice and rats, and inflam matory bone tissues with bone destruction were obtained from adjuvant arthritis rat models. The results showed that (a) both IL-1 receptors (IL-1RI and -II) mRNA were expressed by osteoclasts in all tissue sect ions of normal tibiae; (b) at the stage of the adjuvant arthritis stud ied, the IL-1RI mRNA was the most predominant message in osteoclasts p resent in the area with serious cartilage and bone destruction, wherea s the expression level of IL-1RII mRNA in these osteoclasts was weak; and (c) both IL-1RI and -II mRNA were expressed by osteoblasts, as wel l as by osteocytes localized in the osteoid. In addition, these messag es were also expressed by chondrocytes, but the signals were not detec ted in the chondrocytes in the zones of hypertrophy and provisional ca lcification. Our present study demonstrates for the first time that mo use and rat osteoclasts express IL-1RI and -II mRNA, which suggest tha t a primary effect of IL-1 on osteoclasts may be one of the mechanisms by which IL-1 mediates normal bone remodeling and pathologic bone res orption in chronic inflammatory diseases.