Effects of unfractionated heparin and rivaroxaban on the expression of heparanase and fibroblast growth factor 2 in human osteoblasts

Xia, Jingxin; Sheng, Wei; Pei, Liu-Bao; Li, Ning; Zhang, Zhipeng; Wang, Jialiang; Zu, Jianing; Wang, Nanxiang; Wang, Duanyang

doi:10.3892/mmr.2017.6570

Cited by 10 publications

(3 citation statements)

References 25 publications

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“…It has been reported that the expression of growth factors such as VEGF, HGF, bFGF, FGF-2, and transforming growth factor-β/β1 which play essential roles in EMT, bone formation, angiogenesis, tumor angiogenesis, and renal diseases, are regulated by heparanase. This effect of heparanase is observed in both in vivo and in vitro studies and is through either its enzymatic or non-enzymatic activities [76,168,[175][176][177][178][179][180][181].…”

Section: Heparanase Regulates Gene and Protein Expression And Protein Activationmentioning

confidence: 99%

The Heparanase Regulatory Network in Health and Disease

Mayfosh

Nguyen

Hulett

2021

IJMS

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The extracellular matrix (ECM) is a structural framework that has many important physiological functions which include maintaining tissue structure and integrity, serving as a barrier to invading pathogens, and acting as a reservoir for bioactive molecules. This cellular scaffold is made up of various types of macromolecules including heparan sulfate proteoglycans (HSPGs). HSPGs comprise a protein core linked to the complex glycosaminoglycan heparan sulfate (HS), the remodeling of which is important for many physiological processes such as wound healing as well as pathological processes including cancer metastasis. Turnover of HS is tightly regulated by a single enzyme capable of cleaving HS side chains: heparanase. Heparanase upregulation has been identified in many inflammatory diseases including atherosclerosis, fibrosis, and cancer, where it has been shown to play multiple roles in processes such as epithelial-mesenchymal transition, angiogenesis, and cancer metastasis. Heparanase expression and activity are tightly regulated. Understanding the regulation of heparanase and its downstream targets is attractive for the development of treatments for these diseases. This review provides a comprehensive overview of the regulators of heparanase as well as the enzyme’s downstream gene and protein targets, and implications for the development of new therapeutic strategies.

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Section: Heparanase Regulates Gene and Protein Expression And Protein Activationmentioning

confidence: 99%

The Heparanase Regulatory Network in Health and Disease

Mayfosh

Nguyen

Hulett

2021

IJMS

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“…Indeed, recent studies have shown that bFGF increases osteoclast activity in vitro and that this increasing activity is inhibited by FGFR3-deficient osteoclasts, which revealed the directly positive effect of bFGF-FGFR3 signaling on osteoclast regulation 45 . However, bFGF signaling is also known to affect osteoblast activity 46 . bFGF is expressed in osteoblasts and induces osteogenesis in a stage-specific manner in osteoblastic cells 47 .…”

Section: Discussionmentioning

confidence: 99%

Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis

et al. 2018

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Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3–RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68+ macrophages with high frequency, while pRSK2-expressing CD4+ T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3–RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.

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“…Long-term treatment with glucocorticoids can lead to decreased intestinal calcium absorption, increased urinary calcium excretion, and increased serum thyroid hormones, leading to bone loss [ 13 , 14 ]. Prolonged use of drugs such as proton-pump inhibitors [ 15 ], antiepileptic drugs [ 16 ], diuretics [ 17 ], anticoagulants [ 18 ], and cyclosporine A [ 19 ] can cause severe bone loss. In addition to diseases and drug use, poor living habits, such as alcoholism, smoking, low physical activity, and long-term lack of vitamin intake, can lead to bone loss, which can in turn cause secondary osteoporosis [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus Plantarum HFY15 Helps Prevent Retinoic Acid‐Induced Secondary Osteoporosis in Wistar Rats

Liu

Zheng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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A rat model of secondary osteoporosis was constructed using retinoic acid as an inducer, and the genes, proteins, and bone mass of the rats were analyzed. qPCR detection of the Wnt/β-catenin and OPG/RANK/RANKL signaling pathway-related gene expression levels showed that Lactobacillus plantarum HFY15 played a positive role in regulating both pathways. HFY15 significantly increased β-catenin, Lrp5, Lrp6, Wnt10b, OPG, RANKL, and Runx2 expression and downregulated DKK1, RANK, CTSK, TRACP, and ALP expression. Enzyme-linked immunosorbent assays further confirmed the qPCR results. Tartrate-resistant acid phosphatase staining showed that HFY15 slowed retinoic acid-induced osteoclast formation. Microcomputed tomography showed that HFY15 reduced trabecular separation and increased the percent bone volume, trabecular numbers, trabecular thickness, and bone mineral density in the rats in vivo. These findings indicate that HFY15 may help prevent retinoic acid-induced secondary osteoporosis in vivo.

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Effects of unfractionated heparin and rivaroxaban on the expression of heparanase and fibroblast growth factor 2 in human osteoblasts

Cited by 10 publications

References 25 publications

The Heparanase Regulatory Network in Health and Disease

The Heparanase Regulatory Network in Health and Disease

Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis

Lactobacillus Plantarum HFY15 Helps Prevent Retinoic Acid‐Induced Secondary Osteoporosis in Wistar Rats

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