Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, China.
Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong University, 76 Nanguo Road, Xi'an, 710054, Shaanxi Province, China.
Arthritis Res Ther. 2023 Jun 12;25(1):102. doi: 10.1186/s13075-023-03084-w.
Osteoarthritis (OA) is the most common form of arthritis, affecting millions of aging people. Investigation of abnormal glycosylation is essential for the understanding of pathological mechanisms of OA.
The total protein was isolated from OA (n = 13) and control (n = 11) cartilages. Subsequently, glycosylation alterations of glycoproteins in OA cartilage were investigated by lectin microarrays and intact glycopeptides analysis. Finally, the expression of glycosyltransferases involved in the synthesis of altered glycosylation was assessed by qPCR and GEO database.
Our findings revealed that several glycopatterns, such as α-1,3/6 fucosylation and high-mannose type of N-glycans were altered in OA cartilages. Notably, over 27% of identified glycopeptides (109 glycopeptides derived from 47 glycoproteins mainly located in the extracellular region) disappeared or decreased in OA cartilages, which is related to the cartilage matrix degradation. Interestingly, the microheterogeneity of N-glycans on fibronectin and aggrecan core protein was observed in OA cartilage. Our results combined with GEO data indicated that the pro-inflammatory cytokines altered the expression of glycosyltransferases (ALG3, ALG5, MGAT4C, and MGAT5) which may contribute to the alterations in glycosylation.
Our study revealed the abnormal glycopatterns and heterogeneities of site-specific glycosylation associated with OA. To our knowledge, it is the first time that the heterogeneity of site-specific N-glycans was reported in OA cartilage. The results of gene expression analysis suggested that the expression of glycosyltransferases was impacted by pro-inflammatory cytokines, which may facilitate the degradation of protein and accelerate the process of OA. Our findings provide valuable information for the understanding of molecular mechanisms in the pathogenesis of OA.
骨关节炎（OA）是最常见的关节炎形式，影响着数以百万计的老年人。研究异常糖基化对于理解 OA 的病理机制至关重要。
从 OA（n=13）和对照（n=11）软骨中分离总蛋白。随后，通过凝集素微阵列和完整糖肽分析研究 OA 软骨中糖蛋白的糖基化改变。最后，通过 qPCR 和 GEO 数据库评估参与异常糖基化合成的糖基转移酶的表达。
我们的研究结果表明，OA 软骨中存在几种糖基化模式改变，如α-1,3/6 岩藻糖基化和高甘露糖型 N-聚糖。值得注意的是，在 OA 软骨中，超过 27%的鉴定糖肽（来源于 47 种主要位于细胞外区的糖蛋白的 109 种糖肽）消失或减少，这与软骨基质降解有关。有趣的是，在 OA 软骨中观察到纤连蛋白和聚集蛋白核心蛋白上 N-聚糖的微不均一性。我们的研究结果结合 GEO 数据表明，促炎细胞因子改变了糖基转移酶（ALG3、ALG5、MGAT4C 和 MGAT5）的表达，这可能导致糖基化的改变。
本研究揭示了与 OA 相关的异常糖基化模式和糖基化位点特异性异质性。据我们所知，这是首次报道 OA 软骨中存在糖基化位点特异性 N-聚糖的异质性。基因表达分析结果表明，糖基转移酶的表达受促炎细胞因子的影响，这可能促进蛋白降解并加速 OA 进程。我们的研究结果为理解 OA 发病机制中的分子机制提供了有价值的信息。
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