Upton Maureen L, Chen Jun, Guilak Farshid, Setton Lori A
Department of Biomedical Engineering, Box 90281, 136 Hudson Hall, Duke University, Durham, NC 27708, USA.
J Orthop Res. 2003 Nov;21(6):963-9. doi: 10.1016/S0736-0266(03)00063-9.
Cells of the meniscus are exposed to a wide range of time-varying mechanical stimuli that may regulate their metabolic activity in vivo. In this study, the biological response of the meniscus to compressive stimuli was evaluated in vitro, using a well-controlled explant culture system. Gene expression for relevant extracellular matrix proteins was quantified using real-time RT-PCR following a 24 h period of applied static (0.1 MPa compressive stress) or dynamic compression (0.08-0.16 MPa). Static and dynamic compression were found to differentially regulate mRNA levels for specific proteins of the extracellular matrix. Decreased mRNA levels were observed for decorin ( approximately 2.1 fold-difference) and type II collagen ( approximately 4.0 fold-difference) following 24 h of dynamic compression. Decorin mRNA levels also decreased following static compression ( approximately 4.5 fold-difference), as did mRNA levels for both types I ( approximately 3.3 fold-difference) and II collagen ( approximately 4.0 fold-difference). Following either static or dynamic compression, mRNA levels for aggrecan, biglycan and cytoskeletal proteins were unchanged. It is noteworthy that static compression was associated with a 2.6 fold-increase in mRNA levels for collagenase, or MMP-1, suggesting that the homeostatic balance between collagen biosynthesis and catabolism was altered by the mechanical stimuli. These findings demonstrate that the biosynthetic response of the meniscus to compression is regulated, in part, at the transcriptional level and that transcription of types I and II collagen as well as decorin may be regulated by common mechanical stimuli.
半月板细胞会受到多种随时间变化的机械刺激,这些刺激可能在体内调节其代谢活性。在本研究中,使用控制良好的外植体培养系统在体外评估了半月板对压缩刺激的生物学反应。在施加24小时静态(0.1MPa压缩应力)或动态压缩(0.08 - 0.16MPa)后,通过实时RT-PCR对相关细胞外基质蛋白的基因表达进行定量。发现静态和动态压缩对细胞外基质特定蛋白的mRNA水平有不同的调节作用。动态压缩24小时后,核心蛋白聚糖(差异约2.1倍)和II型胶原蛋白(差异约4.0倍)的mRNA水平下降。静态压缩后核心蛋白聚糖的mRNA水平也下降(差异约4.5倍),I型(差异约3.3倍)和II型胶原蛋白(差异约4.0倍)的mRNA水平同样下降。在静态或动态压缩后,聚集蛋白聚糖、双糖链蛋白聚糖和细胞骨架蛋白的mRNA水平均未改变。值得注意的是,静态压缩与胶原酶或MMP - 1的mRNA水平增加2.6倍相关,这表明机械刺激改变了胶原蛋白生物合成和分解代谢之间的稳态平衡。这些发现表明,半月板对压缩的生物合成反应部分在转录水平受到调节,并且I型和II型胶原蛋白以及核心蛋白聚糖的转录可能受常见机械刺激的调节。