Transforming growth factor-β increases interleukin-6 transcripts in osteoblasts

Bone remodeling is regulated by local factors and cytokines. Among them, interleukin-6 (IL-6) plays a critical role in bone resorption, and its synthesis is stimulated by osteoresorptive factors. Transforming growth factor-β (TGF-β) is present in high amounts in the bone matrix and is a local regulator of bone formation. However, its role in bone resorption remains unclear. In this paper, we report that TGF-β stimulates IL-6 transcripts in a time- and dose-dependent manner in primary rat osteoblasts isolated from 22-day-old calvariae (Ob cells). The TGF-β effect on IL-6 mRNA levels does not require de novo protein synthesis because cycloheximide, a protein synthesis inhibitor, does not block the induction. The mechanisms of IL-6 stimulation by TGF-β is at least partially transcriptional because TGF-β induces IL-6 heterogenous nuclear RNA, and, to a lesser extent, IL-6 transcription rate as determined by a nuclear run-on assay. Transforming growth factor-β upregulation of IL-6 may be critical in conditions of increased bone resorption, such as myeloma.