Li Y, Wang Y, Chubinskaya S, Schoeberl B, Florine E, Kopesky P, Grodzinsky A J
Massachusetts Institute of Technology, Cambridge, MA, USA.
Rush University Medical Center, Chicago, IL, USA.
Osteoarthritis Cartilage. 2015 Feb;23(2):266-74. doi: 10.1016/j.joca.2014.11.006. Epub 2014 Nov 11.
Interleukin-1 is one of the inflammatory cytokines elevated after traumatic joint injury that plays a critical role in mediating cartilage tissue degradation, suppressing matrix biosynthesis, and inducing chondrocyte apoptosis, events associated with progression to post-traumatic osteoarthritis (PTOA). We studied the combined use of insulin-like growth factor-1 (IGF-1) and dexamethasone (Dex) to block these multiple degradative effects of cytokine challenge to articular cartilage.
Young bovine and adult human articular cartilage explants were treated with IL-1α in the presence or absence of IGF-1, Dex, or their combination. Loss of sulfated glycosaminoglycans (sGAG) and collagen were evaluated by the DMMB and hydroxyproline assays, respectively. Matrix biosynthesis was measured via radiolabel incorporation, chondrocyte gene expression by qRT-PCR, and cell viability by fluorescence staining.
In young bovine cartilage, the combination of IGF-1 and Dex significantly inhibited the loss of sGAG and collagen, rescued the suppression of matrix biosynthesis, and inhibited the loss of chondrocyte viability caused by IL-1α treatment. In adult human cartilage, only IGF-1 rescued matrix biosynthesis and only Dex inhibited sGAG loss and improved cell viability. Thus, the combination of IGF-1 + Dex together showed combined beneficial effects in human cartilage.
Our findings suggest that the combination of IGF-1 and Dex has greater beneficial effects than either molecule alone in preventing cytokine-mediated cartilage degradation in adult human and young bovine cartilage. Our results support the use of such a combined approach as a potential treatment relevant to early cartilage degradative changes associated with joint injury.
白细胞介素-1是创伤性关节损伤后升高的炎症细胞因子之一，在介导软骨组织降解、抑制基质生物合成和诱导软骨细胞凋亡中起关键作用，这些事件与创伤后骨关节炎（PTOA）的进展相关。我们研究了胰岛素样生长因子-1（IGF-1）和地塞米松（Dex）联合使用以阻断细胞因子对关节软骨的这些多重降解作用。
在有或没有IGF-1、Dex或其组合存在的情况下，用IL-1α处理幼年牛和成人的关节软骨外植体。分别通过DMMB和羟脯氨酸测定评估硫酸化糖胺聚糖（sGAG）和胶原蛋白的损失。通过放射性标记掺入测量基质生物合成，通过qRT-PCR检测软骨细胞基因表达，并通过荧光染色检测细胞活力。
在幼年牛软骨中，IGF-1和Dex的组合显著抑制了sGAG和胶原蛋白的损失，挽救了基质生物合成的抑制，并抑制了IL-1α处理引起的软骨细胞活力丧失。在成人软骨中，只有IGF-1挽救了基质生物合成，只有Dex抑制了sGAG损失并改善了细胞活力。因此，IGF-1 + Dex组合在人软骨中显示出联合有益作用。
我们的研究结果表明，在预防成人和幼年牛软骨中细胞因子介导的软骨降解方面，IGF-1和Dex的组合比单独使用任何一种分子具有更大的有益作用。我们的结果支持使用这种联合方法作为与关节损伤相关的早期软骨降解变化的潜在治疗方法。
