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Effects of doxycycline on mesenchymal stem cell chondrogenesis and cartilage repair

机译：强力霉素对间充质干细胞软骨形成和软骨修复的影响

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Objective: Strategies to improve cartilage repair tissue quality after bone marrow cell-based procedures may reduce later development of osteoarthritis. Doxycycline is inexpensive, well-tolerated, and has been shown to reduce matrix-metalloproteinases (MMPs) and osteoarthritis progression. This study tests the hypotheses that doxycycline reduces MMP, enhances chondrogenesis of human bone marrow-derived mesenchymal stem cells (hMSC), and improves in vivo cartilage repair. Design: Ninety hMSC pellets were cultured in chondrogenic media with either 0-, 1- or 2-??g/mL doxycycline. Pellets were evaluated with stereomicroscopy, proteoglycan assay, qRT-PCR, and histology. Osteochondral defects (OCDs) were created in the trochlear grooves of 24-Sprague-Dawley rats treated with/without oral doxycycline. Rats were sacrificed at 12-weeks and repair tissues were examined grossly and histologically. Results: hMSC pellets with 1-??g/mL (P = 0.014) and 2-??g/mL (P = 0.002) doxycycline had larger areas than pellets without doxycycline. hMSC pellets with 2-??g/mL doxycycline showed reduced mmp-13 mRNA (P = 0.010) and protein at 21-days. Proteoglycan, DNA contents, and mRNA expressions of chondrogenic genes were similar (P > 0.05). For the in vivo study, while the histological scores were similar between the two groups (P = 0.116), the gross scores of the OCD repair tissues in doxycycline-treated rats were higher at 12-weeks (P = 0.017), reflective of improved repair quality. The doxycycline-treated repairs also showed lower MMP-13 protein (P = 0.029). Conclusions: This study shows that doxycycline improves hMSC chondrogenesis and decreases MMP-13 in pellet cultures and within rat OCDs. Doxycycline exerted no negative effect on multiple measures of chondrogenesis and cartilage repair. These data support potential use of doxycycline to improve cartilage repair to delay the onset of osteoarthritis. ? 2012 Osteoarthritis Research Society International.
机译：目的：基于骨髓细胞的手术后改善软骨修复组织质量的策略可能会减少骨关节炎的发展。强力霉素价格便宜，耐受性好，已被证明可以减少基质金属蛋白酶（MMP）和骨关节炎的进展。这项研究检验了强力霉素可降低MMP，增强人骨髓间充质干细胞（hMSC）软骨形成并改善体内软骨修复的假说。设计：将九十个hMSC沉淀物在软骨形成培养基中用0、1、2或2？g / mL强力霉素进行培养。通过立体显微镜，蛋白聚糖测定，qRT-PCR和组织学评估药丸。在经/未经口服强力霉素治疗的24只Sprague-Dawley大鼠的滑车沟中产生了软骨软骨缺损（OCD）。在第12周处死大鼠，并对修复组织进行大体和组织学检查。结果：与没有强力霉素的颗粒相比，具有1-Δg/ mL（P = 0.014）和2-Δgg/ mL（P = 0.002）的hMSC沉淀具有更大的面积。在21天时，含2-Δεg/ mL强力霉素的hMSC沉淀显示mmp-13 mRNA（P = 0.010）和蛋白质减少。软骨生成蛋白的蛋白聚糖，DNA含量和mRNA表达相似（P> 0.05）。对于体内研究，尽管两组之间的组织学评分相似（P = 0.116），强力霉素治疗的大鼠的强迫症修复组织的总评分在12周时较高（P = 0.017），反映了改善维修质量。用强力霉素治疗的修复物还显示出较低的MMP-13蛋白（P = 0.029）。结论：这项研究表明，强力霉素可改善颗粒培养物中和大鼠强迫症中的hMSC软骨生成并降低MMP-13。强力霉素对软骨生成和软骨修复的多种措施均无负面影响。这些数据支持使用强力霉素改善软骨修复，延缓骨关节炎的发作。 ？ 2012年国际骨关节炎研究学会。

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