Salisbury Palomares Kristy T, Gerstenfeld Louis C, Wigner Nathan A, Lenburg Marc E, Einhorn Thomas A, Morgan Elise F
Boston University and Boston University School of Medicine, Boston, Massachusetts, USA.
Arthritis Rheum. 2010 Apr;62(4):1108-18. doi: 10.1002/art.27343.
To characterize patterns of molecular expression that lead to cartilage formation in vivo in a postnatal setting, by profiling messenger RNA expression across the time course of mechanically induced chondrogenesis.
Retired breeder Sprague-Dawley rats underwent a noncritical-sized transverse femoral osteotomy. Experimental animals (n = 45) were subjected to bending stimulation (60 degrees cyclic motion in the sagittal plane for 15 minutes/day) of the osteotomy gap beginning on day 10 after the operation. Control animals (n = 32) experienced continuous rigid fixation. Messenger RNA isolated on days 10, 17, 24, and 38 after surgery was analyzed using a microarray containing 608 genes involved in skeletal development, tissue differentiation, fracture healing, and mechanotransduction. The glycosaminoglycan (GAG) content in the stimulated tissues was compared with that in native articular cartilage as a means of assessing the progression of chondrogenic development of the tissues.
The majority of the 100 genes that were differentially expressed were up-regulated in response to mechanical stimulation. Many of these genes are associated with articular cartilage development and maintenance, diarthrodial joint development, cell adhesion, extracellular matrix synthesis, signal transduction, and skeletal development. Quantitative real-time polymerase chain reaction results were consistent with the microarray findings. The GAG content of the stimulated tissues increased over time and was no different from that of articular cartilage on day 38 after surgery.
Our findings indicate that mechanical stimulation causes up-regulation of genes that are principally involved in joint cavity morphogenesis and critical to articular cartilage function. Further study of this type of stimulation may identify key signaling events required for postnatal hyaline cartilage formation.
通过分析机械诱导软骨形成过程中整个时间进程的信使核糖核酸（mRNA）表达，来描述在出生后环境中导致体内软骨形成的分子表达模式。
对退役的斯普拉格-道利种大鼠进行非临界尺寸的股骨横向截骨术。实验动物（n = 45）在手术后第10天开始接受截骨间隙的弯曲刺激（矢状面60度循环运动，每天15分钟）。对照动物（n = 32）进行持续刚性固定。使用包含608个参与骨骼发育、组织分化、骨折愈合和机械转导的基因的微阵列，分析术后第10、17、24和38天分离的mRNA。将受刺激组织中的糖胺聚糖（GAG）含量与天然关节软骨中的含量进行比较，作为评估组织软骨形成发育进程的一种方法。
差异表达的100个基因中的大多数在机械刺激下上调。这些基因中的许多与关节软骨发育和维持、滑膜关节发育、细胞粘附、细胞外基质合成、信号转导和骨骼发育有关。定量实时聚合酶链反应结果与微阵列结果一致。受刺激组织的GAG含量随时间增加，在术后第38天与关节软骨的GAG含量无差异。
我们的研究结果表明，机械刺激导致主要参与关节腔形态发生且对关节软骨功能至关重要的基因上调。对这种类型刺激的进一步研究可能会确定出生后透明软骨形成所需的关键信号事件。
