کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3381487 1220258 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutational and functional analyses of xylosyltransferases and their implication in osteoarthritis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی ایمونولوژی، آلرژی و روماتولوژی
پیش نمایش صفحه اول مقاله
Mutational and functional analyses of xylosyltransferases and their implication in osteoarthritis
چکیده انگلیسی

SummaryObjectiveThe hallmark in osteoarthritis (OA) is the loss of proteoglycans (PGs) in articular cartilage (AC). Xylosyltransferase I (XT-I) catalyzes the transfer of xylose to serine residues in the core protein and initiates the biosynthesis of PGs in AC. The XYLT-II gene encodes a highly homologous protein but its biological function is not yet known. Here we investigate for the first time genetic variations in the XYLT-genes and serum XT-I activities and their implication in OA.MethodsDenaturing high-performance liquid chromatography (DHPLC) was used for the screening of the XYLT-genes in 49 OA patients. For a detailed characterization of XT-I amino acid exchanges we performed recombinant expression of XT-I mutants in insect cells. Furthermore, the XT activity was measured in the patients' serum.ResultsThe variation c.1569C > T (XYLT-II) occurs with a significantly higher frequency in younger OA patients in comparison with the older ones (P < 0.001) and the controls (P < 0.02). Furthermore, significantly higher serum XT activities were found in patients with a long disease duration of OA (P < 0.04). The recombinant XT-I mutants p.P385L and p.I552S had reduced enzymatic activity (85% and 74%) compared with the wildtype (wt).ConclusionsOur findings indicate a correlation of the c.1569 T-allele in XYLT-II with an earlier manifestation of OA and that the serum XT activity is a potential biochemical marker for staging and monitoring the progression of AC damage in OA. Comparison of XT-I activity in mutant enzymes in vivo and in vitro revealed that heterozygous mutations are not involved in OA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Osteoarthritis and Cartilage - Volume 14, Issue 5, May 2006, Pages 442–448
نویسندگان
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