MMP8 和 MMP9 的高表达促进了大鼠模型中糖尿病性骨关节炎的进展。
Elevated expression of MMP8 and MMP9 contributes to diabetic osteoarthritis progression in a rat model.
机构信息
Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
Department of Endocrine, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
出版信息
J Orthop Surg Res. 2021 Jan 19;16(1):64. doi: 10.1186/s13018-021-02208-9.
BACKGROUND
Knowledge regarding the pathogenesis of osteoarthritis (OA) is very limited. Previous studies have shown that matrix metalloproteinase (MMP) 8 and MMP9 were upregulated in patients with diabetic OA. However, their regulatory functions and mechanisms in diabetic OA are not fully understood.
METHODS
Diabetic OA rats were constructed using a high-fat diet combined with streptozotocin (STZ) induction. Safranin O-Fast green staining was used to detect the pathological changes in rat knee cartilage. MMP8 and MMP9 overexpression vectors or siRNAs were injected into diabetic OA rats to overexpress or knockdown the expression of MMP8 and MMP9, which was verified by real-time quantitative PCR (RT-qPCR). The expression of MMP8 and MMP9, chondrocyte differentiation markers collagen type II alpha 1 (COL2A1) and collagen type I alpha 1(COL1A1), and antiapoptotic protein BCL2 were detected using immunohistochemistry (IHC), and the number of apoptotic cells was detected by the transferase-mediated d-UTP nick-end-labeling (TUNEL) assay.
RESULTS
High-fat diet combined with STZ-induced rats exhibited joint cartilage damage, morphological changes, and increased expression of MMP8 and MMP9. Overexpression of MMP8 and MMP9 in the joint cavity further aggravated the pathological morphological changes, decreased the expression of COL2A1 and COL1A1, increased the expression of BCL2, and promoted cell apoptosis in diabetic OA rats. The use of siRNA to inhibit MMP8 and MMP9 levels in the cartilage joints significantly reversed the decrease in COL2A1 and COL1A1 expression and partially reversed BCL2 expression and chondrocyte apoptosis.
CONCLUSION
MMP8 and MMP9 promoted rat diabetic OA model. The underlying mechanism may be related to inhibiting cartilage differentiation and promoting chondrocyte apoptosis.
背景
骨关节炎（OA）发病机制的相关知识非常有限。先前的研究表明，基质金属蛋白酶（MMP）8 和 MMP9 在糖尿病性 OA 患者中上调。然而，它们在糖尿病性 OA 中的调节功能和机制尚不完全清楚。
方法
采用高脂饮食联合链脲佐菌素（STZ）诱导构建糖尿病性 OA 大鼠模型。番红 O-fast 绿染色检测大鼠膝关节软骨的病理变化。将 MMP8 和 MMP9 过表达载体或 siRNA 注射到糖尿病性 OA 大鼠体内，以过表达或敲低 MMP8 和 MMP9 的表达，实时定量 PCR（RT-qPCR）验证。采用免疫组织化学（IHC）检测 MMP8 和 MMP9、软骨细胞分化标志物胶原 II 型α1（COL2A1）和胶原 I 型α1（COL1A1）以及抗凋亡蛋白 BCL2 的表达，采用原位末端转移酶标记法（TUNEL）检测凋亡细胞数量。
结果
高脂饮食联合 STZ 诱导的大鼠出现关节软骨损伤、形态学改变以及 MMP8 和 MMP9 表达增加。关节腔中 MMP8 和 MMP9 的过表达进一步加重了糖尿病性 OA 大鼠的病理形态学改变，降低了 COL2A1 和 COL1A1 的表达，增加了 BCL2 的表达，并促进了软骨细胞凋亡。使用 siRNA 抑制软骨关节中 MMP8 和 MMP9 的水平显著逆转了 COL2A1 和 COL1A1 表达的降低，并部分逆转了 BCL2 表达和软骨细胞凋亡。
结论
MMP8 和 MMP9 促进了大鼠糖尿病性 OA 模型的发生。其潜在机制可能与抑制软骨分化和促进软骨细胞凋亡有关。
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