Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4493-4500.
The pathogenesis of osteoarthritis centers on the imbalance between catabolic and anabolic processes in cartilage metabolism. Insulin growth factor 1 (IGF-1) has been shown to have anabolic effects in cartilage in vitro. This study aim to determine whether IGF-1 on cartilage is associated with loss of chondrocyte and extracellular matrix breakdown using the Hartley guinea pig model.
Cartilage from the medial and lateral tibial plateau of 6-month and 12-month old Hartley guinea pigs were used for this study. Histological analysis was performed with hematoxylin-eosin (HE) and toluidine blue staining. Safranin-O staining was used to quantify proteoglycan (PG) loss and the extent of cartilage damage by Modified Mankin score. Distribution of IGF-1 was demonstrated with in situ hybridization techniques. IGF-1 mRNA levels were assessed using Real-time PCR.
Histological loss of chondrocytes, and cartilage matrix and decreased IGF-1 distribution were demonstrated in a temporal and spatial manner. Compared to the 6-month old samples, the 12-month specimens had significantly cartilage degeneration and less cartilage matrix and PGs staining. Decreased level of IGF-1 was also observed in the 12-month samples. These observations were more pronounced in the medial tibial plateau when compared to the lateral plateau.
The decreased level of IGF-1 may play a critical role for maintaining the balance between catabolic and anabolic processes in cartilage metabolism during the development of osteoarthritis. Thus, the increase of IGF-1 may be applicable to developing OA therapy.
骨关节炎的发病机制集中在软骨代谢中分解代谢和合成代谢过程的失衡上。胰岛素样生长因子 1(IGF-1)已被证明在体外对软骨具有合成代谢作用。本研究旨在使用 Hartley 豚鼠模型确定 IGF-1 对软骨是否与软骨细胞丢失和细胞外基质分解有关。
本研究使用了 6 个月和 12 个月大的 Hartley 豚鼠内侧和外侧胫骨平台的软骨。使用苏木精-伊红(HE)和甲苯胺蓝染色进行组织学分析。番红 O 染色用于通过改良 Mankin 评分定量糖胺聚糖(PG)损失和软骨损伤程度。使用原位杂交技术显示 IGF-1 的分布。使用实时 PCR 评估 IGF-1 mRNA 水平。
在时间和空间上均显示出软骨细胞、软骨基质的丢失和 IGF-1 分布减少。与 6 个月大的样本相比,12 个月大的样本的软骨变性明显,软骨基质和 PGs 染色减少。还观察到 12 个月大的样本中 IGF-1 水平降低。与外侧平台相比,内侧胫骨平台的这些观察结果更为明显。
IGF-1 水平的降低可能在骨关节炎发展过程中软骨代谢中分解代谢和合成代谢过程的平衡中起关键作用。因此,增加 IGF-1 可能适用于开发 OA 治疗方法。