THE TRANSCRIPTIONAL CONTROL OF TGF-BETA IN HUMAN OSTEOBLAST-LIKE CELLS IS DISTINCT FROM THAT OF IL-1-BETA

Transforming growth factor β (TGF-β) and interleukin 1 (IL-1) are among the most potent osteotropic cytokines. The expression of mRNA for both TGF-β and IL-1β was studied in human osteoblast-like cells in vitro. These cells constitutively expressed TGF-β but not IL-1β mRNA. Treatment of the cells with the systemic hormones 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] (10-8 M) and parathyroid hormone (10-7 M) induced an increase in TGF-β mRNA but failed to stimulate the production of IL-1-β mRNA. Retinoic acid (10-8 M) had no effect on either mRNA species. The cytokines IL-1α (200 pg/ml), tumour necrosis factor α (TNF-α) (17 ng/ml) and bacterial lipopolysaccharide (LPS) (500 ng/ml) stimulated the production of IL-1β mRNA after 6-8 hours. This was followed by an increase in protein production after 24 hours. In contrast, the production of TGF-β mRNA remained constant after treatment with these agents. Treatment of the cells with hydrocortisone (10-8 M) resulted in the suppression of both TGF-β and IL-1β mRNA. However, when the stimulating agent 1,25-(OH)2D3 was added in conjunction with hydrocortisone the mRNA expression of TGF-β mRNA returned to 70% of the stimulated level. In contrast, the addition of the stimulatory agent IL-1α to hydrocortisone-treated cells resulted in no increase in IL-1β mRNA. In-situ hybridization demonstrated both TGF-β and IL-1β mRNA at the cellular level. These data show that human osteoblasts express TGF-β and IL-1β and that they are differentially modulated by a distinct group of agents. This may reflect the contrasting roles of these cytokines in the control of the bone remodelling cycle. © 1992.