Khan Ilyas M, Evans Sam L, Young Robert D, Blain Emma J, Quantock Andrew J, Avery Nick, Archer Charles W
Cardiff University, Cardiff, UK.
Arthritis Rheum. 2011 Nov;63(11):3417-27. doi: 10.1002/art.30543.
We have discovered that a combination of fibroblast growth factor 2 and transforming growth factor β1 induce profound morphologic changes in immature articular cartilage. The purpose of this study was to test the hypothesis that these changes represent accelerated postnatal maturation.
Histochemical and biochemical assays were used to confirm the nature of the morphologic changes that accompany growth factor stimulation of immature bovine articular cartilage explants in serum-free culture medium. Growth factor-induced apoptosis, cellular proliferation, and changes in the collagen network were also quantitatively analyzed.
Growth factor stimulation resulted in rapid resorption from the basal aspect of immature cartilage explants that was simultaneously opposed by cellular proliferation from the apical aspect driven from a pool of chondroprogenitor cells we have previously described. Maturation-dependent changes in tissue stiffness, collagen crosslinking, and collagen fibril architecture as well as differentiation of the extracellular matrix into distinct pericellular, territorial, and interterritorial domains were all present in growth factor-stimulated cartilage samples and absent in control samples.
Our data demonstrate that it is possible to significantly enhance the maturation of cartilage tissue using specific growth factor stimulation. This may have applications in transplantation therapy or in the treatment of diseased cartilage, through phenotype modulation of osteoarthritic chondrocytes in order to stimulate growth and maturation of cartilage repair tissue.
我们发现成纤维细胞生长因子2和转化生长因子β1的组合可诱导未成熟关节软骨发生显著的形态学变化。本研究的目的是验证这些变化代表出生后加速成熟这一假说。
采用组织化学和生化分析方法，以确认在无血清培养基中生长因子刺激未成熟牛关节软骨外植体时伴随的形态学变化的性质。还对生长因子诱导的细胞凋亡、细胞增殖以及胶原网络的变化进行了定量分析。
生长因子刺激导致未成熟软骨外植体基部迅速吸收，同时顶端的细胞增殖与之对抗，这种增殖由我们之前描述的一群软骨祖细胞驱动。在生长因子刺激的软骨样本中出现了与成熟相关的组织硬度、胶原交联和胶原纤维结构的变化，以及细胞外基质分化为不同的细胞周、区域和区域间结构域，而对照样本中则没有这些变化。
我们的数据表明，使用特定的生长因子刺激可显著促进软骨组织的成熟。这可能在移植治疗或患病软骨治疗中具有应用价值，通过调节骨关节炎软骨细胞的表型来刺激软骨修复组织的生长和成熟。
