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首页> 外文期刊>Journal of orthopaedic research >Osteogenic growth peptide normally stimulated by blood loss and marrow ablation has local and systemic effects on fracture healing in rats.
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Osteogenic growth peptide normally stimulated by blood loss and marrow ablation has local and systemic effects on fracture healing in rats.

机译:通常由失血和骨髓消融刺激的成骨生长肽对大鼠骨折愈合具有局部和全身作用。

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摘要

Osteogenic growth peptide, a histone H4-related, 14-amino-acid peptide, is an active mediator of local, as well as systemic, osteogenic activity in response to marrow ablation, trauma, and blood loss. In this study, the effect of exogenous osteogenic growth peptide on the healing of femoral fractures in rats was investigated. A fracture at the midshaft of the femur was created in 50 rats. Half of the rats were injected subcutaneously with 25 ng of osteogenic growth peptide per rat per day for the first 7 days after fracture. Radiographs were taken each week, and the diameter of the callus was measured. The femurs of four animals from each group were harvested 1, 2, 3, and 4 weeks after fracture. Two femurs from each group were sectioned for histologic examination, and two were sectioned for measurement of density and mineral content. Marrow was aspirated from the contralateral femurs to establish adhering cell cultures, which were examined for osteogenicity. At 2 weeks, a large increase in mitogenicity and osteogenicity was seen in the marrow-derived cultures from the rats treated with osteogenic growth peptide; this increase was sustained through 4 weeks. Extraction of RNA from the contralateral marrow (systemic expression) and callus (local expression) for amplification with reverse transcription-polymerase chain reaction revealed greater systemic expression of transforming growth factors beta1, beta2, and beta3, fibroblast growth factor-2, insulin-like growth factor-1, and aggrecan throughout the 4 weeks after fracture, whereas types IIA and IIB collagen, link protein, and fibroblast growth factor receptor-3 had a greater local expression. The specimens treated with osteogenic growth peptide had a stronger expression of transforming growth factor-beta1, both locally and systemically. The average diameter of the callus was greater for the treated rats at all time intervals, and peak diameters were 7.58 mm at 3 weeks for the treated rats and 6.64 mm at 2 weeks and 6.63 mm at 3 weeks for the controls. Histological study revealed an earlier organization and faster healing of the treated fractures, as evidenced by the larger, earlier appearance of cartilaginous soft callus and the more rapid organization of bridging trabecular bone. No statistical significance was obtained when these comparisons were made between the groups. These results suggest that osteogenic growth peptide can be used to promote earlier proliferation and differentiation of osteogenic cells in marrow and bone-repair callus, possibly through its effect on the transforming growth factor-beta family.
机译:成骨生长肽是一种与组蛋白H4相关的14个氨基酸的肽,是响应于骨髓消融,创伤和失血的局部以及全身性成骨活性的活性介质。在这项研究中,研究了外源性成骨生长肽对大鼠股骨骨折愈合的影响。 50只大鼠在股骨中轴骨折。在骨折后的前7天,每天每只大鼠皮下注射25 ng成骨生长肽。每周进行射线照相,并测量愈伤组织的直径。每组四只动物的股骨在骨折后1、2、3和4周收获。将每组的两个股骨切成切片进行组织学检查,并将两个股骨切成切片以测量密度和矿物质含量。从对侧股骨吸出骨髓以建立粘附细胞培养物,检查其成骨性。在第2周,在用成骨生长肽治疗的大鼠的骨髓培养物中观察到有丝分裂性和成骨性的大量增加;这种增加持续了4周。从对侧骨髓(全身表达)和愈伤组织(局部表达)中提取RNA进行逆转录-聚合酶链反应扩增,发现转化生长因子β1,β2和β3,成纤维细胞生长因子2,胰岛素样蛋白的系统表达更高在骨折后的4周内,其生长因子-1和聚集蛋白聚糖均处于聚集状态,而IIA和IIB型胶原蛋白,连接蛋白和成纤维细胞生长因子受体3则具有更大的局部表达。用成骨生长肽处理的标本在局部和全身均具有更强的转化生长因子-beta1表达。在所有时间间隔,被治疗大鼠的愈伤组织的平均直径均较大,并且被治疗大鼠在3周时的峰值直径为7.58mm,在2周时为对照的峰值直径为6.64mm,而在3周时为对照的峰值直径为6.63mm。组织学研究显示,治疗后的骨折组织更早,愈合更快,软骨软call愈大,外观越早,桥接小梁骨的组织越快,就证明了这一点。在各组之间进行这些比较时,没有统计学意义。这些结果表明,成骨生长肽可以用于促进骨髓和骨修复愈伤组织中成骨细胞的早期增殖和分化,可能是通过其对转化生长因子-β家族的作用。

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