Matrix Metalloproteinase-3 Expression and Structural Changes in Biomechanical Loaded Articular Cartilage

關節軟骨生物機械受力後細胞外基質金屬蛋白酶與結構表現變化

王志龍(Jue-Long Wang) ； 孫淑芬(Shu-Fen Sun) ； 黃巧雯(Chiao-Wen Hwang) ； 林克隆(Ko-Long Lin) ； 許培德(Pei-Te Hsu) ； 王昱菱(Yu-Ling Wang) ； 何正宇(Zhang-Yu Hoe)

《台灣復健醫學雜誌》 39卷4期 (2011/12) Pp. 211-217

https://doi.org/10.6315/2011.39(4)02

摘要

前言：軟骨是承受壓力很好的組織，常給予反覆的機械力會影響軟骨的代謝及活性。軟骨細胞代謝的內部改變可能是導致退化性關節炎的重要因素。雖然軟骨代謝的現象曾被廣泛探討，而啟動其中代謝反應的變化及相關的結構改變中的訊息傳導機制仍不清楚。本研究的目的乃是探討軟骨在受力之後的微結構變化，與受力後細胞外基質金屬蛋白酶（matrix metalloproteinase-3,MMP-3）的變化。方法：本研究分析軟骨在組織培養下接受機械力之後，MMP-3的表現並探討細胞外基質的降解性變化與結構和微結構的改變。軟骨組織切片經由組織培養環境利用FlexorCell系統給予壓力，在0.3Hz，20MPa compressive stress之下作用4小時，將受力前及於受力開始後經4小時、24小時及48小時軟骨之MMP-3表現與控制組進行比較，並將軟骨結構及微結構變化利用Nomarski光學顯微鏡及掃瞄式電子顯微鏡進行觀察。經由此方法，我們探討軟骨在受力之後MMP-3之表現，並探討軟骨在受力之後的微結構變化。結果：本研究結果顯示在受力的軟骨中，相較於控制組會有較高的MMP-3的表現。在受力的關節軟骨，由Nomarski光學顯微鏡可看到破壞性的結構改變，而在電子顯微鏡下可看到受力的軟骨會有軟骨細胞外基質的降解性變化。結論：由本研究，我們發現在生物機械力作用下，關節軟骨之細胞外基質會有降解變化並表現較多的MMP-3。

關鍵字

生物機械力（biomechanical forces） ； 細胞外基質降解性變化（matrix degradation） ； 細胞外基質金屬蛋白酶（matrix metalloproteinase-3） ； 關節軟骨（articular cartilage）

並列摘要

Background: Cartilage functions as a highly successful load-bearing tissue. However, frequent mechanical loading can affect cartilage metabolism and viability significantly. Intrinsic changes in the metabolism of chondrocytes have also been proposed as an important feature of osteoarthritis. Although many aspects of chondrocyte catabolism have been extensively investigated, the signals that initiate such metabolic changes, and their correlation with structural changes, remain unclear. We hypothesized that matrix metaproteinase-3 (MMP-3) may play a significant role. The purpose of this study was to investigate the activity of MMP-3 in cartilage under load, as well as degeneration-related structural changes of the cartilage matrix under load. Method: Tissue blocks of porcine cartilages were prepared for tissue culture, and biomechanical forces were applied with a FlexerCell system. Compressive stress of 20 MPa at 0.3 Hz was induced in the experimental cartilage for 240 minutes. The expression and activity of MMP-3 in the experimental cartilage were measured before and at the time points of 4 hours, 24 hours, and 48 hours after start loading. Cartilage samples without loading were used as a control. Structural and ultrastructural changes in the cartilage were investigated under Normarski light microscopy and scanning electron microscopy. Results: Our results indicated that MMP-3 activity in the loaded cartilages was significantly higher than in the control group. Structural and ultrastructural investigations found evident degradation of the cartilage matrix in loaded cartilages. This study provides information regarding the changes in MMP-3 activity in the loaded cartilages, and the changes in cartilage matrix under load. Conclusion: This study demonstrated that, under biomechanical force, the matrix of articular cartilage was degraded, with a higher expression of MMP-3.

並列關鍵字

biomechanical forces ； matrix degradation ； matrix metalloproteinase-3 ； articular cartilage