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

Bone remodeling is regulated by local factors and cytokines, Among them, in terleukin-6 (IL-6) plays a critical role in bone resorption, and its synthe sis is stimulated by osteoresorptive factors. Transforming growth factor-be ta (TGF-beta) is present in high amounts in the bone matrix and is a local regulator of bone formation, However, its role in bone resorption remains u nclear. In this paper, we report that TGF-beta stimulates IL-6 transcripts in a time- and dose-dependent manner in primary rat osteoblasts isolated fr om 22-day-old calvariae (Ob cells), The TGF-beta effect on IL-6 mRNA levels does not require de novo protein synthesis because cyclohesimide, a protei n synthesis inhibitor, does not block the induction. The mechanisms of IL-6 stimulation by TGF-beta is at least partially transcriptional because TGF- beta induces IL-6 heterogenous nuclear RNA, and, to a lesser extent, IL-6 t ranscription rate as determined by a nuclear run-on assay. Transforming gro wth factor-beta upregulation of IL-6 may be critical in conditions of incre ased bone resorption, such as myeloma, (C) 2000 by Elsevier Science Inc. Al l rights reserved.