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10.1371/journal.pone.0179248 http://scihub22266oqcxt.onion/10.1371/journal.pone.0179248 C5464661!5464661 !28594896     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28594896 &cmd=llinks): Failed to open stream: HTTP request failed! 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Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB |pdf=|usr=}}{{28594896 }} gab.com Text Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28594896 #FOAvip PURPOSE: Bisphosphonates related osteonecrosis of jaw (BRONJ) is a severe complication of systemic BPs administration, the mechanism of which is still unclarified. Recently, platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts was reported to promote angiogenesis and osteogenesis. This study aimed to clarify whether bisphosphonates suppressed preosteoclasts releasing PDGF-BB, and whether the suppression harmed coupling of angiogenesis and osteogenesis, which could contribute to BRONJ manifestation. METHODS AND RESULTS: Zoledronate significantly inhibited osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining and PDGF-BB secretion tested by ELISA. In line with decreasing secretion of PDGF-BB by preosteoclasts exposed to zoledronate, conditioned medium (CM) from the cells significantly induced less migration of endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) compared to CM from unexposed preosteoclasts. Meanwhile, angiogenic function of EPCs and osteoblastic differentiation of MSCs also declined when culturing with CM from preosteoclasts treated by zoledronate (PZ-CM), evidenced by tube formation assay of EPCs and alkaline phosphatase activity of MSCs. Western blot assay showed that the expression of VEGF in EPCs and OCN, RUNX2 in MSCs declined when culturing with PZ-CM compared to CM from preostoeclasts without exposure of zoledronate. CONCLUSION: Our study found that zoledronate was able to suppress preosteoclasts releasing PDGF-BB, resulting in suppression of angiogenesis and osteogenesis. Our study may partly contributed to the mechanism of BRONJ. Twit Text FOAVip Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28594896 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28594896 #FOAvip English Wikipedia <ref>{{Cite pmid|28594896 }}</ref> Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB #MMPMID28594896 Gao SY ; Zheng GS ; Wang L ; Liang YJ ; Zhang SE ; Lao XM ; Li K ; Liao GQ PLoS One 2017[]; 12 (6 ): e0179248 PMID28594896 show ga PURPOSE: Bisphosphonates related osteonecrosis of jaw (BRONJ) is a severe complication of systemic BPs administration, the mechanism of which is still unclarified. Recently, platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts was reported to promote angiogenesis and osteogenesis. This study aimed to clarify whether bisphosphonates suppressed preosteoclasts releasing PDGF-BB, and whether the suppression harmed coupling of angiogenesis and osteogenesis, which could contribute to BRONJ manifestation. METHODS AND RESULTS: Zoledronate significantly inhibited osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining and PDGF-BB secretion tested by ELISA. In line with decreasing secretion of PDGF-BB by preosteoclasts exposed to zoledronate, conditioned medium (CM) from the cells significantly induced less migration of endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) compared to CM from unexposed preosteoclasts. Meanwhile, angiogenic function of EPCs and osteoblastic differentiation of MSCs also declined when culturing with CM from preosteoclasts treated by zoledronate (PZ-CM), evidenced by tube formation assay of EPCs and alkaline phosphatase activity of MSCs. Western blot assay showed that the expression of VEGF in EPCs and OCN, RUNX2 in MSCs declined when culturing with PZ-CM compared to CM from preostoeclasts without exposure of zoledronate. CONCLUSION: Our study found that zoledronate was able to suppress preosteoclasts releasing PDGF-BB, resulting in suppression of angiogenesis and osteogenesis. Our study may partly contributed to the mechanism of BRONJ. |Animals [MESH] |Becaplermin [MESH] |Bone and Bones/cytology [MESH] |Cell Movement/drug effects [MESH] |Cell Survival/drug effects [MESH] |Cells, Cultured [MESH] |Culture Media, Conditioned/pharmacology [MESH] |Diphosphonates/*pharmacology [MESH] |Down-Regulation/drug effects [MESH] |Endothelial Progenitor Cells/cytology/drug effects/metabolism [MESH] |Gene Expression Regulation/drug effects [MESH] |Imidazoles/*pharmacology [MESH] |Male [MESH] |Mesenchymal Stem Cells/cytology/drug effects/metabolism [MESH] |Mice, Inbred C57BL [MESH] |Neovascularization, Physiologic/*drug effects [MESH] |Osteoclasts/drug effects/*metabolism [MESH] |Osteogenesis/*drug effects [MESH] |Proto-Oncogene Proteins c-sis/*metabolism [MESH] |Vascular Endothelial Growth Factor A/metabolism [MESH]Zoledronate suppressed angiogenesis and osteogenesis by inhibiting ost(epmc).pdf DeepDyve Pubget Overpricing