Transforming growth factor-beta 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-beta (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 unclear. In this paper, we report that TGF-beta 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-beta 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-beta is at least partially transcriptional because TGF-beta 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-beta upregulation of IL-6 may be critical in conditions of increased bone resorption, such as myeloma.
Franchimont
N
N
Department of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford, CT, USA. nfranchimont@ulg.ac.be
Rydziel
S
S
Canalis
E
E
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D015850:Interleukin-6 / Q000235:genetics*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D017931:DNA Primers; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta