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Bart's and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary, Centre for Endocrinology, University of London, Charterhouse Square, London EC1M 6BQ, UK

(Correspondence should be addressed to J M Burrin; Email: j.m.burrin{at}qmul.ac.uk)

The aim of the present study was to examine whether triiodo-L-thyronine (T₃) or L-thyroxine (T₄) rapidly activated the mitogen-activated protein kinase (MAPK) intracellular signalling cascade in osteoblast-like cells and investigate whether this activation was initiated at the integrin _Vβ₃ cell surface receptor. Using PCR and western blotting, the expression of integrin _Vβ₃ mRNA and protein was demonstrated in the human osteoblast-like cell lines MG-63 and SaOS-2. The treatment of MG-63 cells with T₃ (10 nM) or T₄ (100 nM) for 10 min stimulated extracellular signal-regulated kinase activity (ERK, a component of the MAPK pathway) as determined by fluorescent immunocytochemistry and an immunocomplex activity assay (T₃ by 10.7-fold, P<0.01 and T₄ by 10.4-fold, P<0.01 compared with control). T₃ (10 nM) and T₄ (100 nM) also significantly stimulated thymidine incorporation into MG-63 cells by 2.3±0.7-fold (P<0.01) and 2.1±0.1-fold (P<0.05) respectively. To establish whether transient ERK activation via the integrin _Vβ₃ cell surface receptor mediated these effects, MG-63 cells were pretreated for 30 min with the specific MAPK kinase inhibitor, U0126 (1 µM), or an anti-integrin _Vβ₃-blocking antibody. Both pretreatments significantly inhibited T₃- and T₄-stimulated ERK activation and abolished T₃-stimulated thymidine incorporation (P<0.01). T₄-stimulated incorporation was significantly inhibited from 2.1- to 1.3-fold above control (P<0.05). Thus, our results suggest that T₃ and T₄ rapidly stimulate ERK activation in MG-63 cells via integrin _Vβ₃ and that one functional effect of this ERK activation is increased DNA synthesis.