Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53705, USA.
J Appl Physiol (1985). 2011 Aug;111(2):552-65. doi: 10.1152/japplphysiol.00073.2011. Epub 2011 May 19.
Ligament heals in a synchronized and complex series of events. The remodeling process may last months or years. Experimental evidence suggests the damaged ligament does not recover its normal functional properties. Specific mechanisms to prevent scar formation and to regenerate the original mechanical function remain elusive but likely involve regulation of creeping substitution. Creeping substitution creates a larger hypercellular, hypervascular, and disorganized granulation tissue mass that results in an inefficient and nonregenerative wound healing process for the ligament. Control of creeping substitution may limit the extent of this tissue compromise and reduce the time necessary for healing. The objective of this study is to better understand the mechanism behind scar formation by identifying the extracellular matrix factors and other unique genes of interest differentially expressed during rat ligament healing via microarray. For this study, rat medial collateral ligaments were either surgically transected or left intact. Ligaments were collected at day 3 or 7 postinjury and used for microarray, quantitative PCR, and/or immunohistochemistry. Results were compared with the normal intact ligament. We demonstrate that early ligament healing is characterized by the modulation of several inflammatory and extracellular matrix factors during the first week of injury. Specifically, a number of matrix metalloproteinases and collagens are differentially and significantly expressed during early ligament healing. Additionally, we demonstrate the modulation of three novel genes, periostin, collagen-triple helix repeat containing-1, and serine protease 35 in our ligament healing model. Together, control of granulation tissue creeping substitution and subsequent downstream scar formation is likely to involve these factors.
韧带在一系列同步且复杂的事件中愈合。重塑过程可能需要数月甚至数年。实验证据表明，受损的韧带无法恢复其正常的功能特性。预防疤痕形成和再生原始机械功能的具体机制仍难以捉摸，但可能涉及爬行替代的调节。爬行替代会产生更大的细胞增多、血管增多和组织混乱的肉芽组织块，导致韧带的愈合过程效率低下且无法再生。通过控制爬行替代，可能会限制组织损伤的程度，并减少愈合所需的时间。本研究的目的是通过识别细胞外基质因子和其他感兴趣的独特基因，通过微阵列更好地了解疤痕形成背后的机制。为此，研究人员通过手术横断或保留大鼠内侧副韧带完整。在损伤后第 3 天或第 7 天收集韧带，用于微阵列、定量 PCR 和/或免疫组织化学分析。将结果与正常完整的韧带进行比较。研究表明，早期韧带愈合的特征是在损伤后的第一周内，几种炎症和细胞外基质因子的调节。具体来说，在早期韧带愈合过程中，有许多基质金属蛋白酶和胶原蛋白差异且显著表达。此外，我们还在我们的韧带愈合模型中证明了三个新基因，骨桥蛋白、三螺旋重复胶原蛋白 1 和丝氨酸蛋白酶 35 的调节。综上所述，控制肉芽组织爬行替代及其随后的下游疤痕形成可能涉及这些因素。
