کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3380238 1220201 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PTHrP overexpression partially inhibits a mechanical strain-induced arthritic phenotype in chondrocytes
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی ایمونولوژی، آلرژی و روماتولوژی
پیش نمایش صفحه اول مقاله
PTHrP overexpression partially inhibits a mechanical strain-induced arthritic phenotype in chondrocytes
چکیده انگلیسی

SummaryObjectiveCell-based tissue engineering strategies are currently in clinical use and continue to be developed at a rapid pace for the repair of cartilage defects. Regardless of the repair methodology, chondrocytes within newly regenerated cartilage remain susceptible to the abnormal inflammatory and mechanical environments that underlie osteoarthritic disease, likely compromising the implant’s integration, function, and longevity. The present study investigates the use of parathyroid hormone-related peptide (PTHrP) overexpression for chondroprotection.DesignBovine articular chondrocytes were transfected with human PTHrP (hPTHrP) constructs (1-141 or 1-173) and subjected to injurious cyclic tensile strain (CTS; 0.5 Hz and 16% elongation) for 48 h. mRNA expression of matrix remodeling, inflammatory signaling, hypertrophic, and apoptotic genes were examined with real-time reverse transcription polymerase chain reaction. Nitric oxide (NO) and prostaglandin E2 (PGE2) production were measured using the Griess assay and enzyme immunoassay (EIA), respectively.ResultsCTS-induced an arthritic phenotype in articular chondrocytes as indicated by increased gene expression of collagenases and aggrecanases and increased production of NO and PGE2. Additionally, CTS increased collagen type X (Col10a1) mRNA expression, whereas overexpression of either hPTHrP isoform inhibited CTS-induced Col10a1 gene expression. However, hPTHrP 1-141 augmented CTS-induced NO and PGE2 production, and neither hPTHrP isoform had any significant effect on apoptotic genes.ConclusionsOur results suggest that chondrocytes overexpressing PTHrP resist mechanical strain-induced hypertrophic-like changes. Therapeutic PTHrP gene transfer may be considered for chondroprotection applications in newly regenerated cartilage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Osteoarthritis and Cartilage - Volume 19, Issue 2, February 2011, Pages 213–221
نویسندگان
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