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首页> 外文期刊>The Journal of Musculoskeletal and Neuronal Interactions >The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in mice
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The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in mice

机译:选择性TrkA激动剂藤黄酰胺可促进成骨细胞分化并改善小鼠骨折愈合

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Objectives: To study effects of the selective TrkA agonist, gambogic amide (GA), on fracture healing in mice and on anosteoprogenitor cell line in vitro. Methods: Mice were given bilateral fibular fractures and treated for two weeks with vehicleor 1 mg/kg/day GA and euthanized at 14-, 21-, and 42-days post-fracture. Calluses were analysed by micro-computedtomography (μCT), three-point bending and histology. For RT-PCR analyses, Kusa O cells were treated with 0.5nM ofGA or vehicle for 3, 7, and 14 days, while for mineralization assessment, cells were treated for 21 days. Results: μCTanalysis found that 21-day GA-treated calluses had both decreased tissue volume (p0.05) and bone surface (p0.05) andincreased fractional bone volume (p0.05) compared to controls. Biomechanical analyses of 42-day calluses revealed thatGA treatment increased stiffness per unit area by 53% (p0.01) and load per unit area by 52% (p0.01). GA treatmentincreased Kusa O gene expression of alkaline phosphatase and osteocalcin (p0.05) by 14 days as well as mineralizationat 21 days (p0.05). Conclusions: GA treatment appeared to have a beneficial effect on fracture healing at 21- and 42-days post-fracture. The exact mechanism is not yet understood but may involve increased osteoblastic differentiation andmatrix mineralization.
机译:目的:研究选择性TrkA激动剂甘布酰胺(GA)对小鼠骨折愈合和体外前体祖细胞系的影响。方法:给小鼠双侧腓骨骨折,并用赋形剂或1 mg / kg / day GA治疗2周,并在骨折后14、21和42天实施安乐死。通过微计算机断层扫描(μCT),三点弯曲和组织学分析愈伤组织。对于RT-PCR分析,用0.5nM的GA或溶媒处理Kusa O细胞3、7和14天,而为了矿化评估,将细胞处理21天。结果:μCT分析发现,与对照组相比,经GA处理21天的愈伤组织既有组织体积减少(p <0.05)和骨表面(p <0.05),又有分数骨体积增加(p <0.05)。 42天老茧的生物力学分析表明,GA处理使单位面积的硬度增加了53%(p <0.01),单位面积的负荷增加了52%(p <0.01)。 GA处理增加了14天的碱性磷酸酶和骨钙素的Kusa O基因表达(p <0.05),并在21天增加了矿化(p <0.05)。结论:GA治疗似乎对骨折后21天和42天的骨折愈合具有有益的作用。确切的机制尚不清楚,但可能涉及成骨细胞分化和基质矿化增加。

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