کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2781729 1153333 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PTH has the potential to rescue disturbed bone growth in achondroplasia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
PTH has the potential to rescue disturbed bone growth in achondroplasia
چکیده انگلیسی

IntroductionAchondroplasia (Ach), the most common form of short-limb short stature, and related disorders are caused by constitutively active point mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Recent studies have provided a large body of evidence for the role of the proliferation and differentiation of chondrocytes in these disorders. Furthermore, a G380R mutation in FGFR3 (FGFR3Ach), which results in achondroplasia, induces apoptosis in the chondrogenic cell line ATDC5. This is associated with a decrease in the expression of PTHrP, which shares the same receptor with PTH, and it is significant that PTHrP rescues these cells from apoptosis.MethodsFetuses derived from transgenic mice expressing FGFR3Ach under the control of the type II collagen promoter (AchTG) or from wild-type mice were obtained on the 15th day of pregnancy. The femurs were collected from these specimens and cultured for 4 days with PTH. The effects of PTH treatment were then determined by morphometric and histological analyses, in situ hybridization of type X collagen mRNA, and the TUNEL assay.ResultsAchTG femurs showed suppressed growth compared with wild type (0.29 ± 0.10 mm vs. 0.46 ± 0.06 mm, respectively; p < 0.05), particularly in cartilage. PTH treatments improved the growth velocity in the femurs of the AchTG (0.50 ± 0.06 mm; p < 0.01 vs. control). This was associated with the inhibition of both differentiation and apoptosis in chondrocytes.ConclusionsOur data suggest that PTH inhibits differentiation and apoptosis in chondrocytes and improves bone growth. These effects thus counterbalance the effects of FGFR3 mutations. PTH therefore is a potential therapeutic agent for achondroplasia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 41, Issue 1, July 2007, Pages 13–18
نویسندگان
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