Evidence for interleukin-1β production by cultured normal human osteoblast-like cells

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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.
Funding Information
  • National Institutes of Health (AG-04875)
  • Training (CA-90441 (Keeting), DK-07352 (Harris))

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