کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1905366 1534709 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A single-point mutation in FGFR2 affects cell cycle and Tgfβ signalling in osteoblasts
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
A single-point mutation in FGFR2 affects cell cycle and Tgfβ signalling in osteoblasts
چکیده انگلیسی

Fgf and Tgfβ are key regulators of bone development. It is not known, however, whether there is a relationship between defective Fgf signalling, resulting in a premature cranial suture fusion, and Tgfβ signalling. We used mouse calvaria osteoblasts carrying a mutation (hFGFR2-C278F) associated with Crouzon and Pfeiffer syndromes to investigate effects of this mutation on cell growth and possible mechanisms underlying it. Mutated osteoblasts displayed reduced S-phase, increased apoptosis and increased differentiation. As Tgfβ signalling appeared to be required in an autocrine/paracrine manner for osteoblast proliferation, we tested the hypothesis that reduced growth might be due, at least in part, to an altered balance between FGF and Tgfβ signalling. Tgfβ expression was indeed decreased in mutated osteoblasts, as compared to osteoblasts carrying the wild type hFGFR2. Treatment with Tgfβ, however, neither increased proliferation in mutated osteoblasts, unlike in controls, nor rescued proliferation in control osteoblasts treated with an Erk1/2 inhibitor. Significantly, Erk2, that is important for proliferation, was reduced relatively to Erk1 in mutated cells. Altogether this study suggests that the hFGFR2-C278F mutation affects the osteoblast ability to respond to Tgfβ stimulation via the Erk pathway and that the overall effect of the mutation is a loss of function.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1802, Issue 3, March 2010, Pages 347–355
نویسندگان
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