Human COL3A1 peptide

Adaptive remodeling processes are essential to the maintenance and viability of coronary artery bypass grafts where clinical outcomes depend strongly on the tissue source. In this investigation, we utilized an ex vivo perfusion bioreactor to culture porcine analogs of common human bypass grafts: the internal thoracic artery (ITA), the radial artery (RA), and the great saphenous vein (GSV), and then evaluated samples acutely (6 h) and chronically (7 days) under in situ or coronary-like perfusion conditions. Although morphologically similar, primary cells harvested from the ITA illustrated lower intimal and medial, but not adventitial, cell proliferation rates than those from the RA or GSV. Basal gene expression levels were similar in all vessels, with only COL3A1, SERPINE1, FN1, and TGFB1 being differentially expressed prior to culture; however, over half of all genes were affected nominally by the culturing process. When exposed to coronary-like conditions, RAs and GSVs experienced pathological remodeling not present in ITAs or when vessels were studied in situ. Many of the remodeling genes perturbed at 6 h were restored after 7 days (COL3A1, FN1, MMP2, and TIMP1) while others (SERPINE1, TGFB1, and VCAM1) were not. The findings elucidate the potential mechanisms of graft failure and highlight strategies to encourage healthy ex vivo pregraft conditioning.

Subacromial impingement is associated with a spectrum of disorders-including rotator cuff disease-but their relationship is complex. We have established a novel murine model of subacromial impingement to study supraspinatus tendinopathy. The purpose of this study was to evaluate changes in gene expression in this murine shoulder impingement model to further elucidate the mechanisms underlying the development of tendinopathy. Twenty-eight C57BL/6 mice were used in this study. All mice underwent bilateral surgery with insertion of a small metal clip in the subacromial space or a sham procedure. The supraspinatus tendons underwent histological analyses, biomechanical testing, and RNA extraction for multiplex gene expression analysis (NanoString, Seattle, WA). Histology demonstrated increased cellularity and disorganized collagen fibers of the supraspinatus tendon in the clip impingement group. Mean load to failure (5.20 vs. 1.50 N, p < 0.001) and mean stiffness (4.95 vs. 1.47 N/mm, p < 0.001) were lower in the impingement group than the sham group. NanoString analyses revealed 111 differentially expressed genes (DEGs) between the impingement and sham groups. DEGs of interest included Mmp3 (expression ratio [ER]: 2.68, p = 0.002), Tgfb1 (ER: 1.76, p = 0.01), Col3a1 (ER: 1.66, p = 0.03), and Tgfbr2 (ER: 1.53, p = 0.01). Statement of clinical significance: We identified 111 DEGs that may contribute to the development of tendinopathy in this model. Further studies of these specific genes will allow identification of their roles in the initiation and regulation of tendon damage, and their potential to serve as novel therapeutic targets in the treatment of rotator cuff disease. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res