Enhancing the biological process of tendon healing under tension by using a collagen matrix patch may improve the ultimate success of rotator cuff repair.
The objective of this study was to determine the primary articular tissue target of doxycycline and minocycline. Synoviocytescartilage cocultures (n ¼ 4) were treated with MMP-13 (25 ng/mL medium) or IL-1 (1.0 ng/mL medium) for 24 h. Doxycycline (4.3, 0.43, 0.043 mM) or minocycline (10, 1.0 or 0.1 mM) were then added and cultures were continued for 96 h. Cartilage and media were analyzed for GAG content. Quantitative PCR was used to measure cartilage MMP-3, MMP-13, aggrecan, COL2A1, ADAMTS-4, and ADAMTS-5 expression, and synoviocyte MMP-3, MMP-13, ADAMTS-4, and ADMATS-5 expression. Total and active MMP-3, MMP-13, and ADAMTS 4/5 enzymes were measured in culture medium. All concentrations of doxycycline and minocycline diminished GAG accumulation in the media. All concentrations of minocycline, but only the highest concentration of doxycycline decreased MMP-3 and MMP-13 expression in synoviocytes but not cartilage, and basal ADAMTS-5 mRNA levels in both synoviocytes and cartilage. Only minocycline decreased active MMP-13 protein in synoviocytes. In summary, the protective effects of tetracycline compounds are more pronounced in synoviocytes than cartilage, and following minocycline compared to doxycycline. Studies to determine the molecular mechanism of action of the tetracyclines in synoviocytes might lead to the design of targeted therapeutics for the treatment of OA or RA. ß
Extensive periosteal stripping (PS) is a risk factor for post-radiation pathologic fracture following surgery for extremity soft tissue tumors. The purpose of this study was to determine the effects of PS on bone structure and mechanical properties. Thirty-one skeletally mature mice underwent PS, with circumferential removal of periosteum from an 8-mm segment of the mid-diaphysis of the left femur. Thirty-one control mice underwent sham surgery in which the femur was isolated without manipulation of the periosteum. At 2, 6, 12, or 26 weeks following surgery, the left femora were examined by micro-CT to quantify cortical thickness (CtTh), cross-sectional area (CSA), bone volume (BV), and polar moment of inertia (PMI). Three-point mechanical bend testing was performed and peak load, stiffness, and energy to failure were determined. PS resulted in significantly decreased CtTh, CSA, BV, and PMI at all time points. Peak load, stiffness, and energy to failure were significantly reduced at 2, 6, and 12 weeks. There were no significant differences in mechanical properties at 26 weeks. In this mouse model, extensive circumferential PS resulted in sustained changes in bone structure that were still evident after 6 months, accompanied by reductions in bone strength that persisted for at least 3 months. ß
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