Down-regulated HS6ST2 in osteoarthritis and Kashin-Beck disease inhibits cell viability and influences expression of the genes relevant to aggrecan metabolism of human chondrocytes

Wang, Wei; Zhong, Bo; Sun, Jian; Cao, Junling; Tian, Juan; Zhong, Nan; Zhao, Wenxiang; Tian, Liang; Xu, Peng; Guo, Dawei; Ju, Xichi; Ma, Wei; Li, Meng; Hou, Weikun; Lu, Shemin

doi:10.1093/rheumatology/ker230

Cited by 22 publications

(22 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there was sGAG staining in the other zones of articular cartilage, suggesting the association of PG loss with cell death during KBD onset in children. In contrast, the depletion of sGAG was observed in the surface and middle zone of articular cartilage from adult KBD patients, similar to that seen in osteoarthritic patients [2, 10]. Therefore, it is now believed that KBD pathology in adults is more like sub-type of OA with a rare aetiology [11] because their pathological and metabolic changes in articular cartilage are quite similar to those observed in OA patients, although some differences in gene expression profiles have been recently reported [12].…”

Section: Proteoglycan Catabolism In Kbdmentioning

confidence: 54%

“…Interestingly, a distinct difference in the loss of PGs from the different zones of articular cartilage was seen between juvenile and adult patients [2, 9, 10]. In the juvenile KBD patients, loss of sulphated GAG (sGAG) staining in articular cartilage was mainly localised to areas within the deep zone where chondrocyte necrosis was observed [2, 9].…”

Section: Proteoglycan Catabolism In Kbdmentioning

confidence: 99%

See 1 more Smart Citation

Proteoglycan metabolism, cell death and Kashin-Beck Disease

et al. 2012

View full text Add to dashboard Cite

Kashin-Beck Disease (KBD) is an endemic, chronic and degenerative osteoarthropathy principally occurring in children. The characteristic pathological change of KBD is chondrocyte necrosis in hyaline articular cartilage. Proteoglycans are one of the major components in the extracellular matrix of articular cartilage, and disrupted proteoglycan metabolism and loss of proteoglycans in articular cartilage from KBD patients has been observed. In this mini-review, we discuss the close relationship between chondrocyte death including necrosis and loss of proteoglycan, and its potential mechanism during KBD onset and development, which may provide new clues for KBD research.

show abstract

Section: Proteoglycan Catabolism In Kbdmentioning

confidence: 54%

Section: Proteoglycan Catabolism In Kbdmentioning

confidence: 99%

Proteoglycan metabolism, cell death and Kashin-Beck Disease

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Aside from cancer, HS6ST2 has also been reported to be involved in embryonic stem cell differentiation (28) and idiopathic pulmonary fibrosis (29). In our previous study, we demonstrated that both the mRNA and protein levels of HS6ST2 were significantly downregulated in the cartilage of patients with osteoarthritis or Kashin-Beck disease (23). In particular, the silencing of HS6ST2 reduced cell viability and altered the expression of cartilage-related genes.…”

Section: Discussionmentioning

confidence: 84%

“…However, the role of HS6ST2 in chondrocyte growth and differentiation is not yet fully understood. In our previous study, we reported that HS6ST2 expression was significantly decreased in the cartilage of patients suffering from osteoarthritis and Kashin-Beck disease and was associated with cell proliferation and Acan metabolism in chondrocytes (23). These data suggest that HS6ST2 is involved in regulating chondrocyte growth.…”

Section: Introductionmentioning

confidence: 78%

Overexpression of heparan sulfate 6-O-sulfotransferase-2 enhances fibroblast growth factor-mediated chondrocyte growth and differentiation

Wang

Sun

et al. 2015

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. In our previous study, we reported that heparan sulfate 6-O-sulfotransferase-2 (HS6ST2) plays an important role in the cartilage of patients with osteoarthritis and Kashin-Beck disease and that it regulates aggrecan (Acan) metabolism and the viability of chondrocytes. However, its role in chondrocyte differentiation remains poorly understood. In the present study, we aimed to investigate the role of HS6ST2 in chondrocyte differentiation in vitro using mouse prechondrocytic cells. We found that the overexpression or silencing of HS6ST2 significantly enhanced or abrogated the effects of fibroblast growth factor (FGF)-2 on chondrocyte growth, respectively. We found that the overexpression of HS6ST2 significantly induced the expression of Acan as well as the amount of total proteoglycans in the prechondrocytic cells in the presence of FGF-2, whereas the silencing of HS6ST2 caused the opposite effect. Furthermore, the expresssion of FGF-2-induced sex-determining region Y-type high mobility group box protein 9 (SOX9), a major transcription factor for chondrocyte proliferation and differentiation, was also enhanced or blocked by HS6ST2 overexpression or HS6ST2 knockdown, respectively. Additionally, Wnt/β-catenin signaling, which inhibited chondrocyte proliferation and differentiation, was suppressed by HS6ST2. Taken together, these data suggest that HS6ST2 plays an important role in regulating chondrocyte growth and differentiation by modulating FGF-2 signaling, thus indicating that it may be a potential and valuable molecular target for the treatment of skeletal dysplasias, such as dwarfism.

show abstract

“…In a previous study at our department, differentially expressed genes (DEGs) in OA cartilage were screened by suppression subtractive hybridization (SSH). SFMBT2 was identified from the reverse subtraction library by sequence analysis and a similarity search with the BLAST programme . We selected this gene for further investigations in this study.…”

Section: Resultsmentioning

confidence: 99%

Down‐regulated in OA cartilage, SFMBT2 contributes to NF‐κB‐mediated ECM degradation

Hussain

Sun

Min

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

The interplay between anabolic and catabolic factors regulates cartilage matrix homoeostasis. In OA, this balance is disrupted which results in cartilage degradation involving a plethora of inflammatory factors. Here, we identify a novel gene “Scm‐like with four MBT domains protein 2” (SFMBT2) negatively regulated in OA cartilage. Articular cartilage from human OA patients undergoing knee arthroplasty surgery exhibited significantly decreased levels of SFMBT2 compared to the normal controls. Down‐regulation of SFMBT2 by specific siRNA disturbed the metabolic homoeostasis and led to decreased expression of anabolic genes (SOX9, COL2A1) while increasing the expression of catabolic genes (MMP13 and ADAMTS4), in human chondrocytes. Finally, we revealed that SFMBT2 intervention by siRNA contributed to the catabolic phenotype of human chondrocytes mediated by NF‐kB pathway.

show abstract

Down-regulated HS6ST2 in osteoarthritis and Kashin-Beck disease inhibits cell viability and influences expression of the genes relevant to aggrecan metabolism of human chondrocytes

Cited by 22 publications

References 43 publications

Proteoglycan metabolism, cell death and Kashin-Beck Disease

Proteoglycan metabolism, cell death and Kashin-Beck Disease

Overexpression of heparan sulfate 6-O-sulfotransferase-2 enhances fibroblast growth factor-mediated chondrocyte growth and differentiation

Down‐regulated in OA cartilage, SFMBT2 contributes to NF‐κB‐mediated ECM degradation

Contact Info

Product

Resources

About