Identification of N-Glycoproteins of Knee Cartilage from Adult Osteoarthritis and Kashin-Beck Disease Based on Quantitative Glycoproteomics, Compared with Normal Control Cartilage

Jing Han; Huan Deng; Yizhen Lyu; Xiang Xiao; Yan Zhao; Jiaxin Liu; Ziwei Guo; Xuan Liu; Lichun Qiao; Hang Gao; Mikko Juhani Lammi

doi:10.3390/cells11162513

Identification of N-Glycoproteins of Knee Cartilage from Adult Osteoarthritis and Kashin-Beck Disease Based on Quantitative Glycoproteomics, Compared with Normal Control Cartilage

Cells. 2022 Aug 12;11(16):2513. doi: 10.3390/cells11162513.

Authors

Jing Han^{1

2}, Huan Deng^{1

2}, Yizhen Lyu^{1

2}, Xiang Xiao^{1

2}, Yan Zhao^{1

2}, Jiaxin Liu^{1

2}, Ziwei Guo^{1

2}, Xuan Liu^{1

2}, Lichun Qiao^{1

2}, Hang Gao³, Mikko Juhani Lammi^{1

4}

Affiliations

¹ Department of Occupational and Environmental Health, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
² Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
³ Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an 710069, China.
⁴ Department of Integrative Medical Biology, Umeå University, 90187 Umeå, Sweden.

Abstract

Glycoproteins are involved in the development of many diseases, while the type and content of N-glycoproteins in the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) are still unclear. This research aims to identify N-glycoproteins in knee cartilage patients with OA and KBD compared with normal control (N) adults. The cartilage samples were collected from gender- and age-matched OA (n = 9), KBD (n = 9) patients, and N (n = 9) adults. Glycoproteomics and label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) obtained N-glycoproteins of KBD and OA. A total of 594 N-glycoproteins and 1146 N-glycosylation peptides were identified. The identified data were further compared and analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interactions (PPI). Pairwise comparison of the glycoproteins detected in the three groups showed that integrin beta-1 (ITGB1), collagen alpha-1 (II) chain (COL2A1), collagen alpha-1 (VII) chain (COL7A1), carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 4 (CHST-4), thrombospondin 2 (THBS2), bone morphogenetic protein 8A (BMP8A), tenascin-C (TNC), lysosome-associated membrane protein (LAMP2), and beta-glucuronidase (GUSB) were significantly differentially expressed. GO results suggested N-glycoproteins mainly belonged to protein metabolic process, single-multicellular and multicellular organism process, cell adhesion, biological adhesion, and multicellular organism development. KEGG and PPI results revealed that key N-glycoproteins were closely related to pathways for OA and KBD, such as phagosome, ECM-receptor interaction, lysosome, focal adhesion, protein digestion, and absorption. These results reflected glycoprotein expression for OA and KBD in the process of ECM degradation, material transport, cell-cell or cell-ECM interaction, and information transduction. These key significantly differentially expressed N-glycoproteins and pathways lead to the degeneration and degradation of the cartilage of OA and KBD mainly by disrupting the synthesis and catabolism of basic components of ECM and chondrocytes and interfering with the transfer of material or information. The key N-glycoproteins or pathways in this research are potential targets for pathological mechanisms and therapies of OA and KBD.

Keywords: Kashin–Beck disease; cartilage; glycoproteins; osteoarthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cartilage, Articular* / metabolism
Chromatography, Liquid
Collagen Type VII / metabolism
Glycoproteins / metabolism
Humans
Kashin-Beck Disease* / genetics
Kashin-Beck Disease* / metabolism
Kashin-Beck Disease* / pathology
Knee
Osteoarthritis* / metabolism
Tandem Mass Spectrometry

Substances

COL7A1 protein, human
Collagen Type VII
Glycoproteins

Grants and funding

This research was supported by the National Natural Science Foundation of China (81872567). The study sponsors did not involve in the study design, data collection, analysis or interpretation, or in the writing of the manuscript, neither did they affect the decision to submit the manuscript for publication.