SETD7 mediates the vascular invasion in articular cartilage and chondrocytes apoptosis in osteoarthriis

Jia, Xiaoshi; Li, Maoquan; Wang, Jiwei; Ning, Jinqiu; Zhao, Ke

doi:10.1096/fj.202000373rrrr

Cited by 17 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In search for factors preventing angiogenesis to use in cancer therapy the line between anti-invasive factors and anti-angiogenic factor became blurred and led to cartilage being commonly accepted as being anti-angiogenic. 1 , 6 - 8 , 10 - 12 , 29 - 32 We confirmed that cartilage explants are not invaded by blood vessels in the CAM assay and that a high salt extract of cartilage matrix inhibited blood vessel attraction. However, our results demonstrated that although not invaded, cartilage explants do attract vessels, indicating that its releasate is pro-angiogenic.…”

Section: Discussionsupporting

confidence: 67%

The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo

et al. 2021

View full text Add to dashboard Cite

Objective Cartilage is avascular and numerous studies have identified the presence of single anti- and pro-angiogenic factors in cartilage. To better understand the maintenance hyaline cartilage, we assessed the angiogenic potential of complete cartilage releasate with functional assays in vitro and in vivo. Design We evaluated the gene expression profile of angiogenesis-related factors in healthy adult human articular cartilage with a transcriptome-wide analysis generated by next-generation RNAseq. The effect on angiogenesis of the releasate of cartilage tissue was assessed with a chick chorioallantoic membrane (CAM) assay as well as human umbilical vein endothelial cell (HUVEC) migration and proliferation assays using conditioned media generated from tissue-engineered cartilage derived from human articular and nasal septum chondrocytes as well as explants from bovine articular cartilage and human nasal septum. Experiments were done with triplicate samples of cartilage from 3 different donors. Results RNAseq data of 3 healthy human articular cartilage donors revealed that the majority of known angiogenesis-related factors expressed in healthy adult articular cartilage are pro-angiogenic. The releasate from generated cartilage as well as from tissue explants, demonstrated at least a 3.1-fold increase in HUVEC proliferation and migration indicating a pro-angiogenic effect of cartilage. Finally, the CAM assay demonstrated that cartilage explants can indeed attract vessels; however, their ingrowth was not observed. Conclusion Using multiple approaches, we show that cartilage releasate has an inherent pro-angiogenic capacity. It remains vessel free due to anti-invasive properties associated with the tissue itself.

show abstract

Section: Discussionsupporting

confidence: 67%

The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In previous studies, SETD7 was shown to be highly expressed in chondrocytes at 20 compared with 1% O 2 ( 13 , 49 ). The present study demonstrated that at 1% O 2 , decreased SETD7 expression leads to inhibition of Hippo signaling and an increase in YAP entering the nucleus.…”

Section: Discussionmentioning

confidence: 85%

“…The thermocycling conditions were set as follows: Initial denaturation for 30 sec at 95°C; followed by 40 cycles of 95°C for 5 sec, 60°C for 30 sec and 95°C for 5 sec; melting at 65°C for 60 sec and 97°C for 1 sec and cooling at 50°C for 30 sec. Relative mRNA expression of target genes was calculated using the 2 −ΔΔCq method ( 13 ). The experiments were performed in triplicate and repeated three times.…”

Section: Methodsmentioning

confidence: 99%

“…Differentiation of chondrocytes and cartilage formation are regulated by a variety of methylases ( 12 ). In our previous study, the lysine methyltransferase Su(var)3-9, enhancer of zeste and trithorax (SET) domain containing 7 (SETD7) regulated apoptosis of chondrocytes at different oxygen partial pressures ( 13 ). SETD7 specifically identifies the K/R-S/T-K* amino acid sequence and transfers a methyl group to lysine residue of K* ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SETD7 regulates chondrocyte differentiation and glycolysis via the Hippo signaling pathway and HIF‑1α

Ning

Wang

et al. 2021

Int J Mol Med

View full text Add to dashboard Cite

Chondrocytes are well adapted to hypoxia and produce more functional extracellular matrix in low oxygen environments in vitro . In our previous study, methyltransferase SET domain containing (SETD)7 regulated chondrocyte activity in hypoxic conditions. However, the precise association between SETD7 and chondrocyte differentiation under low oxygen partial pressure remains unclear. The association between SETD7 and chondrocyte differentiation was studied by silencing SETD7 in chondrocytes in vitro . The results showed that the silencing of SETD7 in ATDC5 cells inhibited the Hippo signaling pathway, decreased Yes-associated protein (YAP) phosphorylation and increased the levels of YAP and hypoxia inducible factor-1α (HIF-1α) in the nucleus. YAP combined with HIF-1α to form a complex that promoted the expression of genes involved in chondrogenic differentiation and the glycolytic pathway. Thus, SETD7 inhibited chondrocyte differentiation and glycolysis via the Hippo signaling pathway. The present study demonstrated that SETD7 was a potential molecular target that maintained the chondrocyte phenotype during cartilage tissue engineering and cartilage-associated disease.

show abstract

“…Interestingly, SETD7 expression is suppressed under hypoxic conditions ( Liu et al, 2015 ). Others have reported that SETD7 is a negative regulator of HIF-1α and downregulates HIF-1α target genes, such as GLUT1, LDHA, PGK1, EPO, PKM2 and VEGF, which are upregulated after SETD7 inhibition ( Li et al, 2021 ; Xiaoshi et al, 2021 ).…”

Section: Setd7-mediated Substrate Modifications and Their Role In Cancermentioning

confidence: 99%

The Epigenetic Regulation of Nonhistone Proteins by SETD7: New Targets in Cancer

Chiang

Heng²,

Zhu³

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Epigenetic modifications are essential mechanism by which to ensure cell homeostasis. One such modification is lysine methylation of nonhistone proteins by SETD7, a mono-methyltransferase containing SET domains. SETD7 methylates over 30 proteins and is thus involved in various classical pathways. As such, SETD7 has been implicated in both the basic functions of normal tissues but also in several pathologies, such as cancers. In this review, we summarize the current knowledge of SETD7 substrates, especially transcriptional-related proteins and enzymes, and their putative roles upon SETD7-mediated methylation. We focus on the role of SETD7 in cancers, and speculate on the possible points of intervention and areas for future research.

show abstract

SETD7 mediates the vascular invasion in articular cartilage and chondrocytes apoptosis in osteoarthriis

Cited by 17 publications

References 43 publications

The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo

The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo

SETD7 regulates chondrocyte differentiation and glycolysis via the Hippo signaling pathway and HIF‑1α

The Epigenetic Regulation of Nonhistone Proteins by SETD7: New Targets in Cancer

Contact Info

Product

Resources

About