Altered Aggrecan Synthesis and Collagen Expression Profiles in Chondrocytes from Patients with Kashin—Beck Disease and Osteoarthritis

Zq, Gao; Guo, Xuewu; Duan, Chaojun; Ma, Wanhong; Xu, Peng; Wang, W; Chen, JC

doi:10.1177/147323001204000411

Cited by 25 publications

(12 citation statements)

References 21 publications

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“…Previous studies have observed that dysfunction of type II collagen contributed to the cartilage lesion of KBD patients. For instance, the expression level of type II collagen in KBD articular cartilage was significantly lower than that in healthy articular cartilage2425. Serum type II collagen can serve as the biomarker of the joint damage of KBD26.…”

Section: Discussionmentioning

confidence: 92%

Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease

Hao

Wang

Wen

et al. 2017

Sci Rep

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Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of growth and development failure of hand of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally including 493 study subjects. Affymetrix Genome Wide Human SNP Array 6.0 was applied for genome-wide SNP genotyping of 90 KBD patients. Association analysis was conducted by PLINK. Imputation analysis was performed by IMPUTE against the reference panel of the 1000 genome project. Two SNPs were selected for replication in an independent validation sample of 403 KBD patients. In the discovery GWAS, significant association was observed between palmar LWR and rs2071358 of COL2A1 gene (P value = 4.68 × 10−8). In addition, GWAS detected suggestive association signal at rs4760608 of COL2A1 gene (P value = 1.76 × 10−4). Imputation analysis of COL2A1 further identified 2 SNPs with association evidence for palmar LWR. Replication study observed significant association signals at both rs2071358 (P value = 0.017) and rs4760608 (P value = 0.002) of COL2A1 gene. Based on previous and our study results, we suggest that COL2A1 was a likely susceptibility gene involved in the hand development failure of KBD.

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Section: Discussionmentioning

confidence: 92%

Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease

Hao

Wang

Wen

et al. 2017

Sci Rep

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“…Articular cartilage ECM consists of a complex mixture of PGs, collagens, aggrecan, and serves an important role in the maintenance of tissue morphogenesis and function 19 . Former studies observed decreased content of PGs and aggrecan in the deep zone of KBD cartilage [20][21][22][23] . In this study, the protein-protein interaction and KEGG pathways analyses indicated that collagens (COL1A1, COL1A2, and COL4A1), were relatively decreased www.nature.com/scientificreports www.nature.com/scientificreports/ in the KBD group.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis

Lei

Amhare

Wang

et al. 2020

Sci Rep

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The pathological mechanism of Kashin-Beck disease (KBD), an endemic osteoarthritic disease, remains to be poorly understood. This study was designed to identify signaling pathways and crucial proteins involved in the pathological mechanism of KBD compared with osteoarthritis (OA). The knee cartilage samples were collected from gender-and age-matched KBD (n = 9) and OA (n = 9) patients. After preprocessing, samples were labeled with Tamdem Mass Tags 6plex multiplex kit, and analyzed by liquid chromatography-tandem mass spectrometry. Proteomic results were analyzed with gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPI). The differential abundance proteins from KBD and OA were validated using western blot analysis. As a result, A total number of 375 proteins were identified to have differential abundance between KBD and OA, of which 121 and 254 proteins were observed to be up-regulated or down-regulated in KBD group. GO analysis shows that the differential abundant proteins are associated with cell junction and signal transducer activity from extracellular to intracellular. KEGG pathways enrichment and PPI network indicate four major pathways, including extracellular matrix -receptor interaction, focal adhesion, phosphatidylinositol 3-kinase (PI3K)-Protein kinase B (Akt), and Ras signaling pathways were involved in the degeneration of cartilage. Moreover, integrins, laminins, NF-κB and other regulative molecules were found as crucial proteins. In conclusion, our results demonstrated that compared with OA, the differential abundance proteins and signaling pathways may contribute to the occurrence and development of joint damage in KBD. Further investigation of their regulative roles and interaction may provide new insights into the pathological mechanisms and therapeutic targets for KBD.Osteoarthritis (OA) is a progressive, degenerative joint disease. It is the major cause of knee pain and locomotor disability worldwide 1,2 . The WHO Scientific Groupon Rheumatic Diseases estimates that 10% of the world's population who are 60 years or older have significant clinical problems attributed to OA 3 . Unlike OA, Kashin-Beck disease (KBD) is a chronic and serious endemic osteoarticular disease, which has been in high prevalence and morbidity in Eastern Siberia of Russia, Northeast China to Sichuan-Tibet Plateau, and North Korea 4,5 . According to the statistics, there were 1.04 billion people in risk of KBD and 0.57 million patients with KBD in China 6 . However, the etiology and pathological mechanisms of KBD are still waiting to be uncovered 7 , which lessen the chances of further effective prevention and treatment measures for the current KBD patients.

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“…Studies with brachymorphic mice, nanomelic chick, dyschondroplastic chicken and Cmd mutant mice clearly show the importance of aggrecan in growth plate cartilage development and skeletogenesis. Furthermore, individuals suffering from Kashin–Beck disease, an endemic osteochondropathy that occurs in certain parts of China, is characterised by small stature and deformities of the limbs and digits, distorted growth plates, chondrocyte apoptosis and low levels of aggrecan [ 37 , 38 , 39 , 40 , 41 ]. The correct sulphation of the CS chains of aggrecan is essential to generate functional determinants capable of interacting with growth factors and morphogens [ 42 , 43 , 44 , 45 ].…”

Section: Cs Sulphation On Aggrecan Is An Important Functional Detementioning

confidence: 99%

Aggrecan, the Primary Weight-Bearing Cartilage Proteoglycan, Has Context-Dependent, Cell-Directive Properties in Embryonic Development and Neurogenesis: Aggrecan Glycan Side Chain Modifications Convey Interactive Biodiversity

Hayes

Melrose

2020

Biomolecules

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This review examines aggrecan’s roles in developmental embryonic tissues, in tissues undergoing morphogenetic transition and in mature weight-bearing tissues. Aggrecan is a remarkably versatile and capable proteoglycan (PG) with diverse tissue context-dependent functional attributes beyond its established role as a weight-bearing PG. The aggrecan core protein provides a template which can be variably decorated with a number of glycosaminoglycan (GAG) side chains including keratan sulphate (KS), human natural killer trisaccharide (HNK-1) and chondroitin sulphate (CS). These convey unique tissue-specific functional properties in water imbibition, space-filling, matrix stabilisation or embryonic cellular regulation. Aggrecan also interacts with morphogens and growth factors directing tissue morphogenesis, remodelling and metaplasia. HNK-1 aggrecan glycoforms direct neural crest cell migration in embryonic development and is neuroprotective in perineuronal nets in the brain. The ability of the aggrecan core protein to assemble CS and KS chains at high density equips cartilage aggrecan with its well-known water-imbibing and weight-bearing properties. The importance of specific arrangements of GAG chains on aggrecan in all its forms is also a primary morphogenetic functional determinant providing aggrecan with unique tissue context dependent regulatory properties. The versatility displayed by aggrecan in biodiverse contexts is a function of its GAG side chains.

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Altered Aggrecan Synthesis and Collagen Expression Profiles in Chondrocytes from Patients with Kashin—Beck Disease and Osteoarthritis

Abstract: Biochemical and morphological mechanisms underlying Kashin-Beck disease and OA include enhanced dedifferentiation and hypertrophy of chondrocytes, increased type I, III and X collagen levels, and suppressed type II collagen and aggrecan production compared with control samples.

Cited by 25 publications

References 21 publications

Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease

Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease

Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis

Aggrecan, the Primary Weight-Bearing Cartilage Proteoglycan, Has Context-Dependent, Cell-Directive Properties in Embryonic Development and Neurogenesis: Aggrecan Glycan Side Chain Modifications Convey Interactive Biodiversity

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