Effect of Zoledronate on the Expression of Vascular Endothelial Growth Factor-A by Articular Chondrocytes and Synovial Cells: An<i>in Vitro</i>Study

Yi, Jin Woong; Lee, Woo Suk; Kim, Sang-Bum; Heo, Youn-Moo; Chae, Dong-Sik

doi:10.11005/jbm.2014.21.4.249

Cited by 7 publications

(3 citation statements)

References 21 publications

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“…Runx2 is a major transcription factor involved in chondrocyte differentiation and is overexpressed in OA cartilage, elevating the production of Col X and MMP13 (28)(29)(30). Angiogenesis is also thought to affect the function and homeostasis of cartilage in the pathogenesis of OA (31). VEGF is a secreted mitogen associated with angiogenesis that has been reported to regulate the vascular invasion of the hypertrophic cartilage in OA; one isoform of which, VEGF-A, promotes subsequent cartilage vascularization (32,33).…”

Section: Discussionmentioning

confidence: 99%

Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway

Ouyang

Jiang

Fang

et al. 2017

Molecular Medicine Reports

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Osteoarthritis (OA) is the most common disease of the joints, and is characterized by the breakdown of cartilage and degradation of the extracellular matrix. OA causes a high level of patient suffering and incurs large societal costs; however, the current strategies for treating OA are restricted due to limited understanding of the underlying molecular and cellular mechanisms. In the present study, the beneficial effects of isoimperatorin (Iso) were investigated using an experimental mouse model of OA, and its mechanism of action on primary chondrocytes was elucidated. Destabilization of the medial meniscus was performed on 8‑week‑old male mice to induce OA in the knees. Iso (500 mg/g/day) was intragastrically administered for 4 weeks. Degeneration of articular cartilage was assessed by histology using the Osteoarthritis Research Society International scoring system. The expression of matrix metalloproteinase (MMP)13, Runt‑related transcription factor (Runx)2, type X collagen (Col X) and vascular endothelial growth factor (VEGF) in the knee joints was examined by immunohistochemistry. In vitro, murine primary chondrocytes were treated with various concentrations of Iso, followed by 10 ng/ml interleukin‑1. The mRNA expression levels of MMP13, Runx2, Col X and VEGF were determined by reverse transcription‑quantitative polymerase chain reaction. The levels of autophagy and mammalian target of rapamycin (mTOR) signaling were determined by western blotting. Iso significantly ameliorated the severity of articular cartilage degradation in mice with experimental OA. The expression levels of MMP13, Runx2, Col X and VEGF were reduced in Iso‑treated mice. In murine primary chondrocytes, Iso also reduced MMP13, Runx2, Col X and VEGF expression, and activated autophagy by downregulating the mTOR complex 1 (mTORC1) signaling pathway. Therefore, the results of the present study demonstrated that Iso ameliorates OA‑induced pathological alterations by delaying chondrocyte deterioration, activating autophagy and inhibiting mTORC1, which suggests that Iso may have therapeutic potential for attenuating articular cartilage degradation and treating OA.

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Section: Discussionmentioning

confidence: 99%

Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway

Ouyang

Jiang

Fang

et al. 2017

Molecular Medicine Reports

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“…[13] Pamidronate and zoledronic acid are the most widely used BPs in oncology and hematology, among the different BPs. [14] RANK ligand inhibitors (denosumab) is a novel antiresorptive agent and inhibit osteoclast function.…”

Section: Discussionmentioning

confidence: 99%

Medication-Related Osteonecrosis of the Jaws (MRONJ) Induced by Incompatible Complete Removable Denture: A Case Report

Gürbüz-Urvasızoğlu¹

2017

IJCOMS

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Abstract:Multiple myeloma is a malignant, hematological neoplasia affected plasma cells. It causes anemia, leads to increased susceptibility to infections by compromising immune response and severe pain is raised as a result of osteolytic lesions. For medical therapy of this condition, bisphosphonates (BPs) can be prescribed. Despite its great benefits in Multiple Myeloma (MM), in particular intravenous administration of BPs can lead to Medication-related osteonecrosis of the jaws (MRONJ). A 61-year-old female patient refers to our department for complaint of difficulty on usage of her prosthesis. In medical history, it was learned that her chemotherapy for multiple myeloma has been continued for 5 years and skull radiographs showed characteristic punched-out lytic lesions. With clinical and radiological examinations, this condition diagnosed as Stage II MRONJ. The aim of this study is to report the case of MRONJ within the reason of incompatible prosthesis by this way to be directive about preventive management.

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“…It plays important roles in neuroprotection (21), angiogenesis (21), fibrogenesis (21), bone matrix mineralization (22), and inflammation (21). Although PEDF was first identified as being produced by retinal pigment epithelium cells, it is now known to be expressed in many tissues and cell types (23), including chondrocytes (24) and synovial cells (25), and it also naturally occurs in the serum (26) and SF (27). In addition to the many beneficial effects that PEDF may exert, it has also been implicated in the pathogenesis of several diseases, such as the chronic inflammatory diseases atherosclerosis (28) and type 2 diabetes (29), as well as certain brain tumors (30).…”

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confidence: 99%

Activation of Complement by Pigment Epithelium–Derived Factor in Rheumatoid Arthritis

Vogt

Talens

Kwasniewicz

et al. 2017

The Journal of Immunology

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The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from the joints, as well as from other tissues, and levels of the complexes did not differ in sera of RA patients and healthy controls. When immobilized, recombinant PEDF expressed in eukaryotic cells activated the classical complement pathway but not the alternative or lectin pathways. C1q protein was demonstrated to bind immobilized PEDF, and PEDF was shown to bind to immobilized C1q, in particular its head regions, which are known to interact with other activators of the classical pathway. Our results call for further investigation into the role of PEDF in inflammatory processes in the joint, which, in combination with classical complement activation, appears to be part of a (patho-)physiologic response.

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Effect of Zoledronate on the Expression of Vascular Endothelial Growth Factor-A by Articular Chondrocytes and Synovial Cells: Anin VitroStudy

Cited by 7 publications

References 21 publications

Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway

Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway

Medication-Related Osteonecrosis of the Jaws (MRONJ) Induced by Incompatible Complete Removable Denture: A Case Report

Activation of Complement by Pigment Epithelium–Derived Factor in Rheumatoid Arthritis

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