Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism
Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test...
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description | Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants released from thrombin-activated platelets on osteoclast-like cell formation in murine bone marrow cultures. Histochemical analysis indicated the presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Transcripts that are characteristically expressed in native osteoclasts were increased in these cultures, as determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition of both cyclooxygenases with indomethacin, as well as the addition of the cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked osteoclast-like cell formation and decreased endogenous prostaglandin E
2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E
2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis. |
doi_str_mv | 10.1016/S8756-3282(02)00697-X |
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2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E
2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis.</description><identifier>ISSN: 8756-3282</identifier><identifier>EISSN: 1873-2763</identifier><identifier>DOI: 10.1016/S8756-3282(02)00697-X</identifier><identifier>PMID: 11996911</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Blood Platelets - metabolism ; Bone marrow culture ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Differentiation - drug effects ; Cell Differentiation - physiology ; Cells, Cultured ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Cyclooxygenase-2 (COX-2) ; Dinoprostone - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression - physiology ; Glycoproteins - genetics ; Glycoproteins - metabolism ; Glycoproteins - pharmacology ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - metabolism ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Membrane Proteins ; Mice ; Mice, Inbred Strains ; NF-kappa B - metabolism ; Osteoclast ; Osteoclasts - cytology ; Osteoclasts - metabolism ; Osteoprotegerin ; Platelet-rich plasma ; Platelets ; Prostaglandin-Endoperoxide Synthases - metabolism ; RANK Ligand ; receptor activator of NF-κB ligand (RANKL) ; Receptor Activator of Nuclear Factor-kappa B ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - metabolism ; Receptors, Tumor Necrosis Factor ; Recombinant Proteins - pharmacology ; RNA, Messenger - analysis ; Skeleton and joints ; Vertebrates: osteoarticular system, musculoskeletal system</subject><ispartof>Bone (New York, N.Y.), 2002-05, Vol.30 (5), p.726-732</ispartof><rights>2002 Elsevier Science Inc.</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-8b42e0b8a6301d7d43cd0748718ff3dc9df4e00e583ad3149cf10314e5ba045f3</citedby><cites>FETCH-LOGICAL-c540t-8b42e0b8a6301d7d43cd0748718ff3dc9df4e00e583ad3149cf10314e5ba045f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S8756-3282(02)00697-X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13672045$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11996911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gruber, R</creatorcontrib><creatorcontrib>Karreth, F</creatorcontrib><creatorcontrib>Fischer, M.B</creatorcontrib><creatorcontrib>Watzek, G</creatorcontrib><title>Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism</title><title>Bone (New York, N.Y.)</title><addtitle>Bone</addtitle><description>Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants released from thrombin-activated platelets on osteoclast-like cell formation in murine bone marrow cultures. Histochemical analysis indicated the presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Transcripts that are characteristically expressed in native osteoclasts were increased in these cultures, as determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition of both cyclooxygenases with indomethacin, as well as the addition of the cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked osteoclast-like cell formation and decreased endogenous prostaglandin E
2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E
2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Platelets - metabolism</subject><subject>Bone marrow culture</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cells, Cultured</subject><subject>Cyclooxygenase 1</subject><subject>Cyclooxygenase 2</subject><subject>Cyclooxygenase-2 (COX-2)</subject><subject>Dinoprostone - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - physiology</subject><subject>Glycoproteins - genetics</subject><subject>Glycoproteins - metabolism</subject><subject>Glycoproteins - pharmacology</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - metabolism</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Membrane Proteins</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>NF-kappa B - metabolism</subject><subject>Osteoclast</subject><subject>Osteoclasts - cytology</subject><subject>Osteoclasts - metabolism</subject><subject>Osteoprotegerin</subject><subject>Platelet-rich plasma</subject><subject>Platelets</subject><subject>Prostaglandin-Endoperoxide Synthases - metabolism</subject><subject>RANK Ligand</subject><subject>receptor activator of NF-κB ligand (RANKL)</subject><subject>Receptor Activator of Nuclear Factor-kappa B</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Receptors, Tumor Necrosis Factor</subject><subject>Recombinant Proteins - pharmacology</subject><subject>RNA, Messenger - analysis</subject><subject>Skeleton and joints</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><issn>8756-3282</issn><issn>1873-2763</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vFDEMhiMEokvhJ4ByAcFh2mQyk2ROVVXxpa4A8SH1FmUTpxvIZJYkU6kH_jsZdkWPlSz78th-7Reh55ScUEL56Tcpet6wVravSfuGED6I5uoBWlEpWNMKzh6i1X_kCD3J-SchhA2CPkZHlA4DHyhdoT9fgi4QoDSpZp3B4jzvIEVddCwZ5-LHeUGwm9Koi58inhyecoHJBJ1LE_wvwAZCyLhs0zRfb7HGu1QJfR10tD6efj3_dLluLOwgWogFj2C2Ovo8PkWPnA4Znh3qMfrx7u33iw_N-vP7jxfn68b0HSmN3HQtkI3UnBFqhe2YsUR0UlDpHLNmsK4DQqCXTFtGu8E4SmqFfqNJ1zt2jF7t51Zdv2fIRY0-L5p1hGnOSlDOecf6e0Eq-0G2YgH7PWjqpTmBU7vkR51uFSVqMUj9M0gt31ekxmKQuqp9Lw4L5s0I9q7r4EgFXh4AnY0OLulofL7jGBdtvalyZ3sO6t9uPCSVjYdowPoEpig7-Xuk_AVb0rAF</recordid><startdate>20020501</startdate><enddate>20020501</enddate><creator>Gruber, R</creator><creator>Karreth, F</creator><creator>Fischer, M.B</creator><creator>Watzek, G</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7X8</scope></search><sort><creationdate>20020501</creationdate><title>Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism</title><author>Gruber, R ; Karreth, F ; Fischer, M.B ; Watzek, G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-8b42e0b8a6301d7d43cd0748718ff3dc9df4e00e583ad3149cf10314e5ba045f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Platelets - metabolism</topic><topic>Bone marrow culture</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - physiology</topic><topic>Cells, Cultured</topic><topic>Cyclooxygenase 1</topic><topic>Cyclooxygenase 2</topic><topic>Cyclooxygenase-2 (COX-2)</topic><topic>Dinoprostone - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression - physiology</topic><topic>Glycoproteins - genetics</topic><topic>Glycoproteins - metabolism</topic><topic>Glycoproteins - pharmacology</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - metabolism</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Membrane Proteins</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>NF-kappa B - metabolism</topic><topic>Osteoclast</topic><topic>Osteoclasts - cytology</topic><topic>Osteoclasts - metabolism</topic><topic>Osteoprotegerin</topic><topic>Platelet-rich plasma</topic><topic>Platelets</topic><topic>Prostaglandin-Endoperoxide Synthases - metabolism</topic><topic>RANK Ligand</topic><topic>receptor activator of NF-κB ligand (RANKL)</topic><topic>Receptor Activator of Nuclear Factor-kappa B</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Receptors, Tumor Necrosis Factor</topic><topic>Recombinant Proteins - pharmacology</topic><topic>RNA, Messenger - analysis</topic><topic>Skeleton and joints</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gruber, R</creatorcontrib><creatorcontrib>Karreth, F</creatorcontrib><creatorcontrib>Fischer, M.B</creatorcontrib><creatorcontrib>Watzek, G</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bone (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gruber, R</au><au>Karreth, F</au><au>Fischer, M.B</au><au>Watzek, G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism</atitle><jtitle>Bone (New York, N.Y.)</jtitle><addtitle>Bone</addtitle><date>2002-05-01</date><risdate>2002</risdate><volume>30</volume><issue>5</issue><spage>726</spage><epage>732</epage><pages>726-732</pages><issn>8756-3282</issn><eissn>1873-2763</eissn><abstract>Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants released from thrombin-activated platelets on osteoclast-like cell formation in murine bone marrow cultures. Histochemical analysis indicated the presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Transcripts that are characteristically expressed in native osteoclasts were increased in these cultures, as determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition of both cyclooxygenases with indomethacin, as well as the addition of the cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked osteoclast-like cell formation and decreased endogenous prostaglandin E
2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E
2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11996911</pmid><doi>10.1016/S8756-3282(02)00697-X</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Blood Platelets - metabolism Bone marrow culture Carrier Proteins - genetics Carrier Proteins - metabolism Cell Differentiation - drug effects Cell Differentiation - physiology Cells, Cultured Cyclooxygenase 1 Cyclooxygenase 2 Cyclooxygenase-2 (COX-2) Dinoprostone - metabolism Fundamental and applied biological sciences. Psychology Gene Expression - physiology Glycoproteins - genetics Glycoproteins - metabolism Glycoproteins - pharmacology Isoenzymes - antagonists & inhibitors Isoenzymes - metabolism Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Membrane Proteins Mice Mice, Inbred Strains NF-kappa B - metabolism Osteoclast Osteoclasts - cytology Osteoclasts - metabolism Osteoprotegerin Platelet-rich plasma Platelets Prostaglandin-Endoperoxide Synthases - metabolism RANK Ligand receptor activator of NF-κB ligand (RANKL) Receptor Activator of Nuclear Factor-kappa B Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism Receptors, Tumor Necrosis Factor Recombinant Proteins - pharmacology RNA, Messenger - analysis Skeleton and joints Vertebrates: osteoarticular system, musculoskeletal system |
title | Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism |
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