Effect of interleukin-1beta on aromatase activity and cell proliferation in human osteoblast-like cells (HOS)

Osteoblast cells have a capacity to produce estrogen from androgen. It is known that inflammatory cytokines in bone increase during estrogen deficiency. In the present study, the effect of interleukin-1beta (IL-1beta) on aromatase (Arom) activity in human osteoblast-like cells (HOS) was investigated. We also investigated the effect of IL-1beta and estradiol (E2) on cell proliferation in HOS. [(3)H] water method was employed to measure Arom activity. Expression of Arom mRNA was determined by the reverse-transcription polymerase chain reaction (RT-PCR) method. The PCR products were confirmed by Southern blot analysis. Cell proliferation was measured by an ELISA-bromo deoxyuridine (BrdU) kit. Addition of IL-1beta increased Arom activity in a dose-dependent manner and addition of IL-1beta (10 ng/ml) resulted in 40% greater activity than control. Addition of 500 ng/ml of human recombinant IL-1 receptor antagonist neutralized the increased Arom activity to control level. Stimulation of Arom mRNA expression by IL-1beta was also found. IL-1beta and E2 stimulate osteoblastic cell proliferation significantly. These findings suggest for the first time that IL-1beta stimulates Arom activity through the IL-1 receptor and also cell proliferation in osteoblast-like cells. It is also demonstrated that this stimulatory effect may be through the IL-1 receptor. Cell proliferation stimulated by IL-1beta was reduced by the addition of the Arom inhibitor fadrozole-HCL (CGS-16949A). These results imply that IL-1beta has a stimulatory effect on estrogen formation and sequentially cell proliferation in bone, and this mechanism may play an important role in osteoblastic function especially in postmenopausal women.