Temporal expression of growth factors and matrix molecules in healing tendon lesions
Temporal expression of growth factors and matrix molecules in healing tendon lesions
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DOI：
10.1016/j.orthres.2004.05.007
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发表时间：
2005-01-01
影响因子：
2.8
通讯作者：
Nixon, AJ
中科院分区：
文献类型：
--
作者：
Dahlgren, LA;Mohammed, HO;Nixon, AJ
过度使用肌腱损伤在精英和休闲运动员中很常见。肌腱愈合可能会提高在细胞水平上通过使用外源性生长因子，但是，鲜为人知的是内源性表达的生长因子在愈合肌腱。本研究描述了胰岛素样生长因子-I（IGF-I）、转化生长因子-β 1（TGF-β 1）和I型和III型胶原在肌腱损伤愈合中的时间表达。在14匹马的双前肢趾上屈肌腱的拉伸区域中创建胶原酶诱导的病变。在损伤后1、2、4、8或24周，从安乐死的马中收获肌腱。使用北方印迹分析（I型和III型胶原）评价基因表达。真实的时间PCR（IGF-I和TGF-β 1）和原位杂交。通过染料结合试验（胶原I型和III型）、放射免疫测定（IGF-I）、ELISA（TGF-β 1）和免疫组织化学测定蛋白质含量。还对样品进行处理以进行差异胶原分型。DNA和糖胺聚糖含量，以及常规H&E染色。显微镜下，损伤从损伤后不久的无定形、无细胞损伤进展为充满胶原纤维和沿沿着张力线组织的成熟成纤维细胞的瘢痕组织。早期病变的特征是生长因子和胶原蛋白的表达立即增加。TGF-β 1的信息水平在伤口愈合过程的早期（1周）达到峰值，而IGF-I的峰值较晚（4周），因为愈合的再生阶段正在进行。在损伤诱导后的前2周，IGF-I蛋白的组织水平实际上比正常肌腱降低了约40%。到4周时，这些水平已超过正常肌腱，并在8周内保持升高。I型和III型胶原蛋白的信使表达在损伤后1周增加，并且在整个研究过程中保持升高。I型胶原蛋白代表研究所有时间点愈合肌腱中的主要胶原蛋白类型。基于这些结果，在损伤后的前2周内外源性给予IGF-I，可通过支持低内源性组织水平和增强个体肌腱成纤维细胞的代谢反应来提供治疗优势。(C)2004骨科研究学会。由爱思唯尔有限公司出版。保留所有权利。
Overuse tendon injuries are common among elite and recreational athletes. Tendon healing may be enhanced at the cellular level through the use of exogenous growth factors; however, little is known about the endogenous expression of growth factors in healing tendon. This study describes the temporal expression of insulin-like growth factor-I (IGF-I), transforming growth factor-beta1 (TGF-beta1), and collagen types I and III in healing tendon lesions. Collagenase-induced lesions were created in the tensile region of the flexor digitorum supeificialis tendon of both forelimbs of 14 horses. Tendons were harvested from euthanatized horses 1, 2, 4 8 or 24 weeks following injury. Gene expression was evaluated using Northern blot analysis (collagen types I and III). real time PCR (IGF-I and TGF-beta1), and in situ hybridization. Protein content was assayed by dye-binding assay (collagen types I and III), radioimmunoassay (IGF-I), ELISA (TGF-beta1), and immunohistochemistry. Samples were also processed for differential collagen typing. DNA and glycosaminoglycan content, and routine H&E staining. Microscopically, lesions progressed from an amorphous, acellular lesion soon after injury to scar tissue filled with collagen fibers and mature fibroblasts organized along lines of tension. Early lesions were characterized by immediate increases in expression of growth factors and collagen. Message levels for TGF-beta1 peaked early in the wound healing process (1 week), while IGF-I peaked later (4 weeks), as the regenerative phase of healing was progressing. In the first 2 weeks after lesion induction, tissue levels of IGF-I protein actually decreased approximately 40% compared to normal tendon. By 4 weeks, these levels had exceeded those of normal tendon and remained elevated through 8 weeks. Message expression for collagen types I and III increased by I week following injury and remained elevated throughout the Course of the study. Collagen type I represented the major type of collagen in healing tendon at all time points of the Study. Based on these results, IGF-I, administered exogenously during the first 2 weeks following Injury, may provide a therapeutic advantage by bolstering low endogenous tissue levels and enhancing the metabolic response of individual tendon fibroblasts. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.