Applying an excessive mechanical stress alters the effect of subchondral osteoblasts on chondrocytes in a co-culture system

Applying an excessive mechanical stress alters the effect of subchondral osteoblasts on chondrocytes in a co-culture system
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DOI:
10.1111/j.1600-0722.2010.00710.x
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发表时间:
2010-04-01
影响因子:
1.9
通讯作者:
Tanne, Kazuo
Tanne, Kazuo
中科院分区:
医学4区
文献类型:
--
作者:
Lin, Yu-Yu;Tanaka, Nobuaki;Tanne, Kazuo

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骨关节炎(OA)有时是由于功能障碍所涉及的反复微创伤造成的,这可能导致软骨下骨的微骨折。这项体外研究的目的是评估软骨下成骨细胞在承受重复过度机械应力时对覆盖软骨细胞代谢的影响。对从猪下颌髁突获得的培养成骨细胞施加 15 kPa(30 个周期 min-1)的高强度循环拉伸应力。然后将藻酸盐珠中的软骨细胞与机械应激或未应激的成骨细胞共培养。与未受应激的成骨细胞共培养的软骨细胞表现出向肥大软骨细胞的表型转变,其特征是II型胶原、聚集蛋白聚糖、Sry相关HMG盒(SOX-9)和软骨寡聚基质蛋白(COMP)基因的表达减少,而X型胶原和骨唾液蛋白(BSP)基因的表达增加,表明共培养可能在一定程度上改变软骨细胞的分化。这些变化在与过度机械应激的成骨细胞共培养的软骨细胞中更为明显。与应激成骨细胞共培养后,软骨细胞中基质金属蛋白酶(MMP)1、MMP3和MMP13基因的表达也增强,DNA、蛋白多糖和胶原蛋白的合成显着减少。这些结果表明,应激的成骨细胞可以诱导软骨代谢的改变,这为 OA 的发病和进展提供了可能的解释。
Osteoarthritis (OA) sometimes occurs as a consequence of repeated microtrauma involved in parafunction, which may lead to microfracture in the subchondral bone. The aim of this in vitro study was to evaluate the effects of subchondral osteoblasts in loading with repeated excessive mechanical stress on the metabolism of overlying chondrocytes. A high-magnitude cyclic tensile stress of 15 kPa (30 cycles min-1) was applied to the cultured osteoblasts obtained from porcine mandibular condyles. The chondrocytes in alginate beads were then co-cultured with mechanically stressed or unstressed osteoblasts. Chondrocytes co-cultured with unstressed osteoblasts showed a phenotypic shift to hypertrophic chondrocytes, characterized by decreased expression of type II collagen, aggrecan, Sry-related HMG box (SOX-9), and cartilage oligomeric matrix protein (COMP) genes and increased expression of type X collagen and bone sialoprotein (BSP) genes, suggesting that the co-culture may change the chondrocyte differentiation to some extent. These changes were more distinct in chondrocytes co-cultured with excessively mechanically stressed osteoblasts. After co-culture with stressed osteoblasts, the expressions of matrix metalloproteinase (MMP)1, MMP3 and MMP13 genes were also enhanced and the synthesis of DNA, proteoglycan and collagen were significantly decreased in chondrocytes. These results demonstrate that alterations in cartilage metabolism can be induced by stressed osteoblasts, indicating a possible explanation for the onset and progression of OA.