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首页> 外文期刊>Osteoarthritis and cartilage >FGF-2 is bound to perlecan in the pericellular matrix of articular cartilage, where it acts as a chondrocyte mechanotransducer.
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FGF-2 is bound to perlecan in the pericellular matrix of articular cartilage, where it acts as a chondrocyte mechanotransducer.

机译：FGF-2在关节软骨的细胞周围基质中与Perlecan结合，在其中它起着软骨细胞机械转导的作用。

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OBJECTIVE: We have shown previously that cutting or loading articular cartilage resulted in a fibroblast growth factor-2 (FGF-2) dependent activation of the extracellularly regulated kinase (ERK), and induction of a number of chondrocyte regulatory proteins including tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases 1 and 3. An extracellular matrix-bound pool of FGF-2 was apparent, which could be liberated from the tissue by heparitinase (Vincent et al., Proc Natl Acad Sci U S A 2002;99(12):8259-64, Vincent et al., Arthritis Rheum 2004 Feb;50(2):526-33). Our objectives were to determine where FGF-2 was stored in articular cartilage, to which proteoglycan it was bound, and to elucidate its role in chondrocyte mechanotransduction. METHODS: Immunohistochemistry and confocal microscopy were used to localise FGF-2 in the tissue. In vitro binding studies were performed using IASYS surface plasmon resonance. To study the role of pericellular FGF-2 in mechanotransduction cartilage explants or articular chondrocytes encapsulated in alginate were loaded using an in house loading rig. The loading response was assessed by the activation of ERK, in the presence or absence of a specific FGFR inhibitor. RESULTS: Here we have identified perlecan as the heparan sulphate proteoglycan that sequesters FGF-2 in articular cartilage. Perlecan and FGF-2 co-localised within the type VI collagen-rich pericellular matrix of porcine and human articular cartilage. Chondrocytes encapsulated in alginate were able to accumulate pericellular perlecan and FGF-2 in culture, and deliver an FGF-dependent activation of ERK when loaded. CONCLUSION: Loading-induced ERK activation was dependent upon the presence and concentration of pericellular FGF-2, suggesting a functional role for this matrix-bound growth factor in chondrocyte mechanotransduction.
机译：目的：我们先前已经表明，切割或加载关节软骨会导致成纤维细胞生长因子2（FGF-2）依赖性的细胞外调节激酶（ERK）活化，并诱导许多软骨细胞调节蛋白，包括金属蛋白酶组织抑制剂-1和基质金属蛋白酶1和3。FGF-2的胞外基质结合池很明显，可以通过肝素酶从组织中释放出来（Vincent等人，Proc Natl Acad Sci USA 2002; 99（12）：8259 -64，Vincent等人，Arthritis Rheum 2004 Feb; 50（2）：526-33）。我们的目标是确定FGF-2储存在关节软骨中的位置，结合到哪个蛋白聚糖上，并阐明其在软骨细胞机械转导中的作用。方法：采用免疫组织化学和共聚焦显微镜在组织中定位FGF-2。使用IASYS表面等离振子共振进行了体外结合研究。为了研究细胞周围FGF-2在机械转导软骨外植体或封装在藻酸盐中的关节软骨细胞的作用，使用室内装载装置进行装载。在存在或不存在特定FGFR抑制剂的情况下，通过激活ERK评估负荷反应。结果：在这里我们已经确定了perlecan是硫酸乙酰肝素蛋白聚糖，它能隔离关节软骨中的FGF-2。 Perlecan和FGF-2共定位在猪和人关节软骨的VI型胶原蛋白丰富的细胞周围基质中。囊封在藻酸盐中的软骨细胞能够在培养物中积聚细胞周膜的Perlecan和FGF-2，并在加载时传递FGF依赖性的ERK激活。结论：负荷诱导的ERK激活取决于细胞周围FGF-2的存在和浓度，提示该基质结合生长因子在软骨细胞机械转导中的功能性作用。

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