Effects of loading on chondrocyte hypoxia, <scp>HIF</scp>‐1α and <scp>VEGF</scp> in the mandibular condylar cartilage of young rats

Yu, Jia; Liang, Feixin; Huang, Hao; Pirttiniemi, Pertti; Yu, Dahai

doi:10.1111/ocr.12212

Cited by 17 publications

(20 citation statements)

References 33 publications

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“…Module 2 including hub gene insulinlike growth factor 1 (IGF1) and vascular endothelial growth factor (VEGF) was associated with "platelet degranulation", "protein processing", "regulation of protein secretion" and "apoptotic signaling pathway". These results are consistent with the previous studies indicating that mechanical loading directly induce weight-bearing area hypoxia followed by upregulated expression of VEGF [32], Shear stress induced the activation of IGF1 pathway which involved in the regulation of morphology and proliferation in the chondrocytes [33], and even IGF-1 has been shown to protect chondrocytes from apoptosis [34]. [35,36].…”

Section: Discussionsupporting

confidence: 93%

Bioinformatics analysis reveals different gene expression patterns in chondrocytes from knee and finger joints: implications for the effect of mechanical stress in the osteoarthritic development

Mei

Yin

Shi

et al. 2020

Preprint

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Background Mechanical stress has been well known to be a significant risk factor for the onset and progression of osteoarthritis (OA). The objective of this study is to clarify the key genes and the signaling pathways which is associated with the effect of mechanical stress on OA development. Results A total of 213 Differentially expressed genes (DEGs) were identified in cultured chondrocytes from knee and finger joints, including 101 up- and 112 down-regulated genes, which brought an enrichment in positive or negative regulation of cell proliferation, positive regulation of cell division, positive regulation of apoptotic process and embryonic limb morphogenesis. Two comparison cohorts shared 122 overlapping genes including 49 up- and 73 down-regulated genes, which enriched in DNA replication, cell division, calcium ion binding and positive regulation of apoptotic process. Twelve hub overlapped genes including Cyclin dependent kinase 1 (CDK1), Kinesin family member 11 (KIF11), Mitotic checkpoint serine/threonine kinase (BUB1) and Mitotic arrest deficient 2 like 1 (MAD2L1) were defined and predicted miRNAs of the genes mainly enriched in Transforming growth factor beta (TGF-β) signaling pathway, Wnt signaling pathway and Mitogen activated kinase-like protein (MAPK) signaling pathway. Conclusions Mechanical stress shown multiple influences on chondrocytes, physiologically necessary for maintaining chondrocyte homeostasis and promoting cartilage development, pathologically help for cartilage destruction and OA development via boosting chondrocyte differentiation and hypertrophy and accelerating cell apoptosis.

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Section: Discussionsupporting

confidence: 93%

Bioinformatics analysis reveals different gene expression patterns in chondrocytes from knee and finger joints: implications for the effect of mechanical stress in the osteoarthritic development

Mei

Yin

Shi

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Hypoxyprobe-1, a type of pimonidazole hydrochloride, was used asa specific marker for hypoxia [ 14 ]. The immunohistochemistry results showed that the expression areas for Hypoxyprobe-1 and HIF-1α ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Hypoxia is not only a consequence of unrestrained fast tumor growth; it also plays a vital role in promoting tumor proliferation, invasion, EMT, distant metastasis and resistance to therapy [ [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] ]. The tumor stroma is a dynamic environment, which includes inflammatory cells, pancreatic stellate cells (PSC), endothelial cells, extracellular matrix (ECM), growth factors and cytokines.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia aggravates microenvironment hypoxia and promotes the metastatic ability of pancreatic cancer

Liang

Qian

et al. 2018

Computational and Structural Biotechnology Journal

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BackgroundDiabetes mellitus and pancreatic cancer are intimately related. Our previous studies showed that high levels of blood glucose promote epithelial-mesenchymal transition of pancreatic cancer. In this study, we evaluated the relationship between hyperglycemia and hypoxic tumor microenvironments.MethodsHIF-1α expression was evaluated by immunohistochemistry in clinical pancreatic cancer tissues with or without diabetes mellitus. Statistcal analysis was performed to explore the relationship between HIF-1α expression and pathological features of patients with pancreatic cancer. In vivo and in vitro models was established to detect whether a hyperglycemia environment could cause hypoxia in the pancreatic parenchyma and promote pancreatic cancer. In addition, we also tested the effect of HIF-1α siRNA on the high glucose-induced invasive and migratory abilities of BxPC-3 cells in culture.ResultOur data showed that pancreatic cancer patients with diabetes had a higher level of HIF-1α expression as well as biliary duct invasion and larger tumor volumes than individuals in the euglycemic group. Diabetic nude mice treated with streptozotocin (STZ) exhibited larger tumors and were more likely to develop liver metastasis than control mice. Acinar cells of the pancreas in diabetic mice showed an obvious expansion of the endoplasmic reticulum and increased nuclear gaps as well as chromatin close to the cellular membrane in some acinar cells. The expression area for Hypoxyprobe-1 and HIF-1α in the diabetic orthotopic xenograft group was larger than that in the control group. The expression level of HIF-1α in the BxPC-3 cancer cell line increased in response to high glucose and CoCl2 concentrations. The high glucose-induced invasive ability, migratory capacity and MMP-9 expression were counter-balanced by siRNA specific to HIF-1α.ConclusionOur results demonstrate that the association between hyperglycemia and poor prognosis can be attributed to microenvironment hypoxia in pancreatic cancer.

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“…The pathogenesis and pathophysiology of OA remain unclear, which creates obstacles in studying the development and progression of OA ( 9 ). Numerous studies have reported on the involvement of VEGF in the degenerative progression of cartilage ( 19 – 21 ). Angiogenic inhibitors are produced by normal articular cartilage, which, consequently, lack vascular tissue ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

Local intra‑articular injection of vascular endothelial growth factor accelerates articular cartilage degeneration in rat osteoarthritis model

et al. 2018

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In the pathophysiology of osteoarthritis (OA), articular cartilage degeneration exhibits a significant role. Vascular endothelial growth factor (VEGF) is considered to be an effective angiogenic factor and a crucial regulator of articular cartilage degeneration in the development of OA. Therefore, the present study aimed to investigate the underlying influences of exogenous VEGF on articular cartilage degeneration in OA model rat. A total of 24 male Sprague-Dawley rats were randomly allocated into 3 groups. In the normal saline (NS) and VEGF groups, animals received bilateral anterior cruciate ligament (ACL) transection to establish the OA model; at 4 weeks post-surgery, the rats received local intra-articular injections of 100 µl NS or VEGF solution, respectively, every week for 4 weeks. The Control group received neither surgery nor injections. All animals were sacrificed at 12 weeks following surgery. Prominent cartilage degeneration was observed in rats in the NS- and VEGF-injected groups. The extent and the grade of cartilage damage in the VEGF-injected group were notably more severe compared with those in the NS-treated group. Western blotting results demonstrated that the expression levels of aggrecan and type II collagen were significantly reduced in OA model rats that were treated with VEGF. In addition, the expression levels of matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (a disintegrin and metalloproteinase; ADAMTS)-4, −5 and −12, type III collagen and transforming growth factor-β1 were significantly increased following VEGF administration. Results from the present study indicated that VEGF may exhibit a promoting role in the development of OA by destroying articular cartilage matrix.

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Effects of loading on chondrocyte hypoxia, HIF‐1α and VEGF in the mandibular condylar cartilage of young rats

Abstract: Mechanical loading seems to directly induce weight-bearing area hypoxia followed by new vessel formation, which indicates that these factors are related and important for the development of cartilage.

Cited by 17 publications

References 33 publications

Bioinformatics analysis reveals different gene expression patterns in chondrocytes from knee and finger joints: implications for the effect of mechanical stress in the osteoarthritic development

Bioinformatics analysis reveals different gene expression patterns in chondrocytes from knee and finger joints: implications for the effect of mechanical stress in the osteoarthritic development

Hyperglycemia aggravates microenvironment hypoxia and promotes the metastatic ability of pancreatic cancer

Local intra‑articular injection of vascular endothelial growth factor accelerates articular cartilage degeneration in rat osteoarthritis model

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