Chetkina E V, Pul A R
Vestn Ross Akad Med Nauk. 2008(5):15-21.
The objective of this study was to determine whether a peptide of type II collagen which can induce collagenase activity can also induce chondrocyte differentiation (hypertrophy) in articular cartilage. At high but naturally occurring concentrations (10 microM and up) the collagen peptide CB12-II induced an increase in the expressions of MMP-13 (24h) and cleavage of type II collagen by collagenase in the mid zone (day 4) and also in the superficial zone (day 6). Furthermore the peptide induced an increase in proliferation on day 1 in the mid and deep zones extending to the superficial zone by day 4. There was also upregulation of COL10A1 expression at day 4 and of type X staining in the mid zone extending to the superficial zone by day 6. Apoptopic cell death was increased by day 4 in the lower deep zone and also in the superficial zone at day 7. The increase in apoptosis in the deep zone was also seen in controls. Our results show that the induction of collagenase activity by cryptic peptide sequence of type II collagen is accompanied by chondrocyte hypertrophy and associated cellular and matrix changes. This induction occurs in the mid and superficial zones of previously healthy articular cartilage. This response of the chondrocyte to a cryptic sequence of denaturated type II collagen may play a role in naturally occurring hypertrophy in endochondral ossification and in the development of cartilage pathology in osteoarthritis.
本研究的目的是确定一种能诱导胶原酶活性的II型胶原蛋白肽是否也能诱导关节软骨中的软骨细胞分化(肥大)。在高浓度但自然存在的浓度(10 microM及以上)下,胶原肽CB12-II在中层区域(第4天)和表层区域(第6天)诱导MMP-13表达增加(24小时)以及胶原酶对II型胶原的切割。此外,该肽在第1天诱导中层和深层区域的增殖增加,并在第4天延伸至表层区域。在第4天COL10A1表达上调,在第6天中层区域的X型染色延伸至表层区域。在第4天,深层下部区域的凋亡细胞死亡增加,在第7天表层区域也增加。在对照组中也观察到深层区域凋亡增加。我们的结果表明,II型胶原蛋白的隐蔽肽序列诱导胶原酶活性的同时伴随着软骨细胞肥大以及相关的细胞和基质变化。这种诱导发生在先前健康的关节软骨的中层和表层区域。软骨细胞对变性II型胶原蛋白隐蔽序列的这种反应可能在软骨内骨化的自然肥大以及骨关节炎软骨病理发展中起作用。