Jenniskens Y M, Koevoet W, de Bart A C W, Weinans H, Jahr H, Verhaar J A N, DeGroot J, van Osch G J V M
Erasmus MC, University Medical Centre Rotterdam, Department of Orthopaedics, The Netherlands.
Osteoarthritis Cartilage. 2006 Nov;14(11):1136-46. doi: 10.1016/j.joca.2006.04.002. Epub 2006 May 24.
Examine effects of insulin-like growth factor 1 (IGF1), transforming growth factor beta2 (TGFbeta2) and fibroblast growth factor 2 (FGF2) on proteoglycan and collagen network and biomechanical properties of the newly formed cartilage matrix.
Bovine articular chondrocytes were cultured in alginate beads for 3 weeks with or without FGF2, TGFbeta2 or IGF1 in the presence of 10% FCS. Proteoglycan content, collagen content, hydroxylysylpyridinoline cross-links and overall matrix metalloproteinase (MMP) activity in the culture medium were measured. Alginate disks cultured for 5 weeks were used to evaluate the effect of growth factors on mechanical properties of the construct by determining the equilibrium aggregate modulus and secant modulus.
IGF1 increased collagen and proteoglycan deposition. FGF2 mainly decreased collagen deposition and TGFbeta2 proteoglycan deposition. A decrease in cross-links was observed in matrix produced by chondrocytes cultured in the presence of TGFbeta2. IGF1 and FGF2 had no influence on the number of cross-links per collagen molecule. Overall MMP activity was significantly higher in culture medium of cells cultured with FGF2. TGFbeta2 and IGF1 had no effect on MMP activity. After 35 days of culture, the matrix produced under influence of IGF1 had a lower permeability and a trend to increase stiffness. FGF2 showed a trend to lower both properties. TGFbeta2 had no effect on these parameters.
IGF1, TGFbeta2 and FGF2 had differential effects on collagen network formation. Of the three growth factors tested, IGF1 seems to be best in promoting the formation of a functional collagen network since it increased proteoglycan and collagen deposition and improved the mechanical properties.
研究胰岛素样生长因子1（IGF1）、转化生长因子β2（TGFβ2）和成纤维细胞生长因子2（FGF2）对蛋白聚糖、胶原网络以及新形成的软骨基质生物力学特性的影响。
将牛关节软骨细胞在含10%胎牛血清（FCS）的条件下，于藻酸盐珠中培养3周，添加或不添加FGF2、TGFβ2或IGF1。测定培养基中的蛋白聚糖含量、胶原含量、羟赖氨酰吡啶交联以及总体基质金属蛋白酶（MMP）活性。将培养5周的藻酸盐圆盘用于通过测定平衡聚集体模量和割线模量来评估生长因子对构建体力学性能的影响。
IGF1增加了胶原和蛋白聚糖的沉积。FGF2主要降低了胶原沉积，而TGFβ2降低了蛋白聚糖沉积。在TGFβ2存在下培养的软骨细胞产生的基质中观察到交联减少。IGF1和FGF2对每个胶原分子的交联数量没有影响。在FGF2培养的细胞培养基中，总体MMP活性显著更高。TGFβ2和IGF1对MMP活性没有影响。培养35天后，在IGF1影响下产生的基质具有较低的渗透性，并且有增加硬度的趋势。FGF2显示出降低这两种特性的趋势。TGFβ2对这些参数没有影响。
IGF1、TGFβ2和FGF2对胶原网络形成具有不同的影响。在所测试的三种生长因子中，IGF1似乎在促进功能性胶原网络形成方面表现最佳，因为它增加了蛋白聚糖和胶原沉积并改善了力学性能。
