Bonassar L J, Grodzinsky A J, Srinivasan A, Davila S G, Trippel S B
Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.
Arch Biochem Biophys. 2000 Jul 1;379(1):57-63. doi: 10.1006/abbi.2000.1820.
The development and maintenance of healthy joints is a complex process involving many physical and biological stimuli. This study investigates the interaction between insulin-like growth factor-I (IGF-I) and static mechanical compression in the regulation of articular cartilage metabolism. Bovine cartilage explants were treated with concentrations of IGF-I from 0 to 300 ng/ml in the presence or absence of 0-50% static compression, and the transient and steady-state incorporation of [(3)H]proline and [(35)S]sulfate into matrix components were measured. In parallel studies, cartilage explants were treated with 0-300 ng/ml IGF-I at media pH ranging from 6.4 to 7.2 and the steady-state incorporation of [(3)H]proline and [(35)S]sulfate was measured. The effect of 50% static compression on IGF-I transport was determined by measuring the uptake of (125)I-labeled IGF-I into cartilage explants. Static compression decreased both [(3)H]proline and [(35)S]sulfate incorporation in a dose-dependent manner in the presence or absence of IGF-I. IGF-I increased [(3)H]proline and [(35)S]sulfate incorporation in a dose-dependent manner in the presence or absence of compression, but the anabolic effect of the growth factor was lessened when the tissue was compressed by 50%. The response of cartilage explants to IGF-I was similarly lessened in unstrained tissue cultured in media at pH 6.4, a condition which results in a similar intratissue pH to that when cartilage is compressed by 50%. The characteristic time constant (tau) for IGF-I stimulation of cartilage explants was approximately 24 h, while tau for inhibition of biosynthesis by static compression was approximately 2 h. Samples which were both compressed and treated with IGF-I demonstrated an initial decrease in biosynthetic activity at 2 h, followed by an increase at 24 h. Static compression did not alter tau for (125)I-labeled IGF-I transport into cartilage but decreased the concentration of (125)I-labeled IGF-I in the tissue at equilibrium.
健康关节的发育和维持是一个复杂的过程，涉及许多物理和生物刺激。本研究调查胰岛素样生长因子-I（IGF-I）与静态机械压缩在调节关节软骨代谢中的相互作用。在存在或不存在0-50%静态压缩的情况下，用浓度为0至300 ng/ml的IGF-I处理牛软骨外植体，并测量[(3)H]脯氨酸和[(35)S]硫酸盐向基质成分的瞬时和稳态掺入。在平行研究中，在pH值为6.4至7.2的培养基中用0-300 ng/ml IGF-I处理软骨外植体，并测量[(3)H]脯氨酸和[(35)S]硫酸盐的稳态掺入。通过测量(125)I标记的IGF-I进入软骨外植体的摄取量来确定50%静态压缩对IGF-I转运的影响。在存在或不存在IGF-I的情况下，静态压缩均以剂量依赖的方式降低[(3)H]脯氨酸和[(35)S]硫酸盐的掺入。在存在或不存在压缩的情况下，IGF-I均以剂量依赖的方式增加[(3)H]脯氨酸和[(35)S]硫酸盐的掺入，但当组织被50%压缩时，生长因子的合成代谢作用减弱。在pH 6.4的培养基中培养的未受拉伸的组织中，软骨外植体对IGF-I的反应同样减弱，这种条件导致组织内pH与软骨被50%压缩时相似。IGF-I刺激软骨外植体的特征时间常数（tau）约为24小时，而静态压缩抑制生物合成的tau约为2小时。同时受到压缩并接受IGF-I处理的样本在2小时时生物合成活性最初下降，随后在24小时时增加。静态压缩未改变(125)I标记的IGF-I转运到软骨中的tau，但在平衡时降低了组织中(125)I标记的IGF-I的浓度。
