Mechanical compression of articular cartilage induces chondrocyte proliferation and inhibits proteoglycan synthesis by activation of the ERK pathway: implications for tissue engineering and regenerative medicine.
Mechanical compression of articular cartilage induces chondrocyte proliferation and inhibits proteoglycan synthesis by activation of the ERK pathway: implications for tissue engineering and regenerative medicine.
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DOI：
10.1002/term.146
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发表时间：
2009-02
影响因子：
3.3
通讯作者：
Reddi, A. Hari
中科院分区：
文献类型：
--
作者：
Ryan, James A.;Eisner, Eric A.;DuRaine, Grayson;You, Zongbing;Reddi, A. Hari
关键词：
关节软骨难以进行内源性修复和再生，因此是组织工程和再生医学策略的焦点。关节软骨组织工程的先决条件是了解创伤或疾病期间机械压缩所涉及的信号转导途径。我们试图探索细胞外信号调节激酶 1/2 (ERK 1/2) 通路在急性机械压迫后软骨细胞增殖和蛋白聚糖合成中的作用。使用和不使用 ERK 1/2 通路抑制剂 PD98059 培养牛关节软骨外植体。软骨外植体以 1 秒的应变速率静态加载 40% 应变，持续 5 秒。对照外植体在类似条件下培养但不上样。存在四个实验组：1)无负载，无抑制剂；2)无负载，有抑制剂PD98059；3)负载，无抑制剂；4)负载有抑制剂PD98059。外植体培养时间不同，从 5 分钟到 5 天不等。然后通过生化和免疫组织化学方法分析外植体。机械压迫诱导 ERK 1/2 磷酸化，并且 ERK 1/2 通路抑制剂 PD98059 以剂量依赖性方式减弱这种磷酸化。机械压缩可增加软骨细胞增殖。这种作用被 ERK 1/2 通路抑制剂阻断。机械压缩还导致蛋白聚糖合成减少，抑制剂 PD98059 可逆转这一现象。总之，ERK 1/2 通路参与急性静态机械压缩后软骨细胞的增殖和生物合成反应。
Articular cartilage is recalcitrant to endogenous repair and regeneration and thus a focus of tissue engineering and regenerative medicine strategies. A pre-requisite for articular cartilage tissue engineering is an understanding of the signal transduction pathways involved in mechanical compression during trauma or disease. We sought to explore the role of the extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway in chondrocyte proliferation and proteoglycan synthesis following acute mechanical compression. Bovine articular cartilage explants were cultured with and without the ERK 1/2 pathway inhibitor PD98059. Cartilage explants were statically loaded to 40% strain at a strain rate of 1−sec for 5 seconds. Control explants were cultured under similar conditions but were not loaded. There were four experimental groups: 1) no load without inhibitor 2) no load with the inhibitor PD98059, 3) loaded without the inhibitor, and 4) loaded with the inhibitor PD98059. Explants were cultured for varying durations, from 5 minutes to 5 days. Explants were then analyzed by biochemical and immunohistochemical methods. Mechanical compression induced phosphorylation of ERK 1/2, and this was attenuated with the ERK 1/2 pathway inhibitor PD98059 in a dose-dependent manner. Chondrocyte proliferation was increased by mechanical compression. This effect was blocked by the inhibitor of the ERK 1/2 pathway. Mechanical compression also led to a decrease in proteoglycan synthesis that was reversed with inhibitor PD98059. In conclusion, the ERK 1/2 pathway is involved in the proliferative and biosynthetic response of chondrocytes following acute static mechanical compression.
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影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
2.4
作者：
Ewers, BJ;Jayaraman, VM;Haut, RC
通讯作者：
Haut, RC
DOI：
10.1097/00003086-200110001-00009
发表时间：
2001-10-01
影响因子：
4.2
作者：
D'Lima, DD;Hashimoto, S;Lotz, MK
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影响因子：
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作者：
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通讯作者：
Kulyk, WM