Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China.
Mol Med Rep. 2012 Jul;6(1):39-44. doi: 10.3892/mmr.2012.863. Epub 2012 Apr 10.
Mitochondria are not only the main energy generators of the cell, but also mediate several critical biochemical processes such as apoptosis, proliferation and redox homeostasis. As such, mitochondrial dysfunctions can lead to a wide variety of human diseases, including cancer and osteoarthritis (OA). In OA, mitochondrial-associated signaling has been implicated in the molecular events leading to cartilage degradation, including oxidative stress, defective chondrocyte biosynthesis and growth responses, increased cytokine-induced chondrocyte inflammation and matrix catabolism, cartilage matrix calcification and increased chondrocyte apoptosis. Thus, the mitochondrial genome represents an attractive target for molecular therapy and OA research has focused on determining its role in chondrocyte metabolism and subsequent cartilage degradation. In this study, we analyzed the mitochondrial gene expression changes that characterize chondrocytes in OA using the Human Mitochondria RT² Profiler™ PCR Array. Twenty-six differentially expressed genes were identified that discriminated chondrocytes in OA from those in normal cartilage, including 17 upregulated and 9 downregulated genes. These genes represent diverse functional categories, including mitochondrial membrane polarization and potential, mitochondrial transport, small molecule transport, targeting proteins to the mitochondria, mitochondrial protein import, outer and inner membrane translocation, mitochondrial fission and fusion, mitochondrial localization and apoptosis. Western blot analysis confirmed that the p53 upregulated modulator of apoptosis (PUMA; encoded by the BB3 gene) was significantly upregulated in OA cartilage. In conclusion, our study generates a differential mitochondrial gene expression profile for chondrocytes in OA and demonstrates that mitochondrial genome dysregulation occurs in cartilage cells during OA. Finally, our results indicate that PUMA may be a new diagnostic and therapeutic target for OA.
线粒体不仅是细胞的主要能量生成器，还介导几种关键的生化过程，如细胞凋亡、增殖和氧化还原稳态。因此，线粒体功能障碍可导致多种人类疾病，包括癌症和骨关节炎 (OA)。在 OA 中，线粒体相关信号转导已被牵连到导致软骨降解的分子事件中，包括氧化应激、软骨细胞生物合成和生长反应缺陷、细胞因子诱导的软骨细胞炎症和基质分解代谢增加、软骨基质钙化和软骨细胞凋亡增加。因此，线粒体基因组是分子治疗的一个有吸引力的靶点，OA 研究集中于确定其在软骨细胞代谢和随后软骨降解中的作用。在这项研究中，我们使用 Human Mitochondria RT² Profiler™ PCR Array 分析了 OA 中特征性软骨细胞的线粒体基因表达变化。鉴定出 26 个差异表达的基因，这些基因可区分 OA 软骨细胞和正常软骨细胞，包括 17 个上调和 9 个下调基因。这些基因代表了多种功能类别，包括线粒体膜极化和电位、线粒体转运、小分子转运、靶向蛋白到线粒体、线粒体蛋白输入、外膜和内膜易位、线粒体分裂和融合、线粒体定位和细胞凋亡。Western blot 分析证实，p53 上调凋亡调节因子 (PUMA；由 BB3 基因编码) 在 OA 软骨中显著上调。总之，我们的研究为 OA 软骨细胞生成了一个差异的线粒体基因表达谱，并表明在 OA 中，线粒体基因组失调发生在软骨细胞中。最后，我们的结果表明，PUMA 可能是 OA 的一个新的诊断和治疗靶点。
