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Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differentiation of osteoblasts from mesenchymal stem cells (MSCs) is an integral part of bone development and homeostasis, and may when improperly regulated cause disease such as bone cancer or osteoporosis. Using unbiased high-throughput methods we here characterize the landscape of global changes in gene expression, histone modifications, and DNA methylation upon differentiation of human MSCs to the osteogenic lineage. Furthermore, we provide a first genome-wide characterization of DNA binding sites of the bone master regulatory transcription factor Runt-related transcription factor 2 (RUNX2) in human osteoblasts, revealing target genes associated with regulation of proliferation, migration, apoptosis, and with a significant overlap with p53 regulated genes. These findings expand on emerging evidence of a role for RUNX2 in cancer, including bone metastases, and the p53 regulatory network. We further demonstrate that RUNX2 binds to distant regulatory elements, promoters, and with high frequency to gene 3' ends. Finally, we identify TEAD2 and GTF2I as novel regulators of osteogenesis.
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PMID:The regulatory landscape of osteogenic differentiation. 2489 11

Osteosarcoma (OS) is the most common bone cancer in children and young adults. The etiology of osteosarcoma is currently unknown. Besides the predominant osteoblasts, the presence of cartilage forming chondrocytes within its tumor tissues suggests a role of chondrogenesis in osteosarcoma development. Runx2 is a master transcription factor both for osteoblast differentiation and for chondrocyte maturation. Interestingly, RUNX2 has been shown to directly interact with p53 and Rb1, two genes essential for osteosarcoma development in mice. However the in vivo relevance of Runx2 during osteosarcoma progression has not been elucidated. We have recently shown that targeting Runx2 expression in hypertrophic chondrocytes delays chondrocyte maturation. It has also been shown that osteoblast-specific deletion of p53 and Rb1 genes developed osteosarcoma in mice. Here, we report our recent research findings using these osteosarcoma mouse models as well as human osteosarcoma tissues. We have detected high-level RUNX2 expression in human osteoblastic osteosarcoma, while chondroblastic osteosarcoma is predominant with chondroid matrix. To minimize the effect of strain difference, we have backcrossed osterix-Cre mice onto congenic FVB/N genetic background. We also detected low-GC content (36%) in sequence around the floxed Rb1 gene and demonstrated that addition of BSA into the reaction system increases the efficiency of PCR genotyping of floxed Rb1 gene. Finally, we successfully generated multiple osteosarcoma mouse models with or without Runx2 transgenic background. These mice showed heterogeneous osteosarcoma phenotypes and marker gene expression. Characterization of these mice will facilitate understanding the role of Runx2 in osteosarcoma pathogenesis and possibly, for osteosarcoma treatment.
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PMID:Research findings working with the p53 and Rb1 targeted osteosarcoma mouse model. 2495 78

Patients with bone cancer metastasis suffer from unbearable pain and bone fractures due to bone remodeling. This is caused by tumor cells that disturb the bone microenvironment. Here, we have investigated the role of tumor-secreted sugar-binding protein, i.e., galectin-3, on osteoblast differentiation and report that it downregulates the expression of osteoblast differentiation markers, e.g., RUNX2, SP7, ALPL, COL1A1, IBSP, and BGLAP, of treated human fetal osteoblast (hFOB) cells. Co-culturing of hFOB cells with human breast cancer BT-549 and prostate cancer LNCaP cells harboring galectin-3 has resulted in inhibition of osteoblast differentiation by the secreted galectin-3 into culture medium. The inhibitory effect of galectin-3 was found to be through its binding to Notch1 in a sugar-dependent manner that has led to accelerated Notch1 cleavage and activation of Notch signaling. Taken together, our findings show that soluble galectin-3 in the bone microenvironment niche regulates bone remodeling through Notch signaling, suggesting a novel bone metastasis therapeutic target.
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PMID:Galectin-3 inhibits osteoblast differentiation through notch signaling. 2542 68

Osteosarcoma (OS) is the most common pediatric bone cancer in children and young adults. Previous studies have suggested the importance of osteoblast activity in OS tumorigenesis and metastasis, as OS is characterized by abnormal bone formation, while osteoblast is the predominant cell type both in OS and in metastatic tumor tissues. RUNX2 is a known essential transcription factor for osteoblast differentiation. RUNX2 has also been linked to many human cancers, including bone cancers and cancer metastasis in bone. However, the view of RUNX2 during OS tumorigenesis has not been unanimous. In this manuscript, we reviewed the osteoblastic origin in OS etiology. The oncogenic property of RUNX2 in human OS studies was briefly summarized. RUNX2 may be involved in OS pathogenesis by regulating cell cycle controlling of (pre)-osteoblasts, which subsequently convert to OS cells. The roles and mechanisms of RUNX2 during OS metastasis and bone metastasis in target cancers (herein prostate and breast cancers), were as described. The potential involvement of Runx2 in multiple mouse OS models that use human OS cell lines (Xenografts), tumor suppressor genes p53 and Rb1 were also discussed. Finally, we updated some microRNAs studies and their relation with RUNX2 in OS pathogenesis. This review provides a comprehensive understanding of RUNX2's function during OS pathogenesis and will help with the research designing and strategy in controlling OS.
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PMID:RUNX2 and Osteosarcoma. 2573 72