Rifas, Leonard

Abstract To determine if bone cells produce interleukin-1β (IL-1β), a potent bone resorption-stimulating agent, we studied well-characterized, nearly homogeneous cultures of normal human osteoblast-like (hOB) cells. With four strains of such cells, vehicle-treated cultures produced minimal IL-1β (mean ± SEM, 1.3 ± 0.3 pg/ml per 106 cells per 24 h) and showed dose-dependent (r = 0.99) increases to 2.2 ± 0.7, 5.0 ± 0.9, or 17.8 ± 6.7 pg/ml, respectively, after treatment with lipopolysaccharide (LPS) at 3, 10, or 30 μg/ml (for increases after 10 and 30 μg/ml treatments, P < 0.05). After treatment with tumor necrosis factor α (TNF-α at 10 U/ ml, IL-1β increased to 16.2 * 3.7 pg/ml (P < 0.05). Neither 17β-estradiol nor bovine parathyroid hormone(1–34) (each at 10 nM), alone or in combination with LPS or TNF-α, affected IL-1β release. Northern blot analysis of total cellular RNA preparation revealed a single hybridization band at 1.9 kb when probed with a partially deleted cDNA for human IL-1β. The steady-state IL-1β mRNA levels showed a significant increase with LPS treatment and a lesser increase with TNF-α treatment in hOB cells. Moreover, TNF-α produced an even greater increase in IL-1 mRNA in HOBIT cells, a well-differentiated clonal cell line derived from normal hOB cells transfected with the SV40 large T antigen. We conclude that human cells of the osteoblast lineage produce IL-Iβ in response to well-recognized stimuli for IL-1 release from responsive tissue. Therefore, IL-1 may play an important role in the local regulation of bone remodeling.