Impaired Osteoclast Formation in Bone Marrow Cultures of Fgf2 Null Mice in Response to Parathyroid Hormone
Fibroblast growth factor (FGF)-2 and parathyroid hormone (PTH) are potent inducers of osteoclast (OCL) formation, and PTH increases FGF-2 mRNA and protein expression in osteoblasts. To elucidate the role of endogenous FGF-2 in PTH responses, we examined PTH-induced OCL formation in bone marrow cultu...
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| Veröffentlicht in: | The Journal of biological chemistry 2003-06, Vol.278 (23), p.21258-21266 |
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| container_title | The Journal of biological chemistry |
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| creator | Okada, Yosuke Montero, Aldemar Zhang, Xuxia Sobue, Takanori Lorenzo, Joseph Doetschman, Thomas Coffin, J. Douglas Hurley, Marja M. |
| description | Fibroblast growth factor (FGF)-2 and parathyroid hormone (PTH) are potent inducers of osteoclast (OCL) formation, and PTH increases FGF-2 mRNA and protein expression in osteoblasts. To elucidate the role of endogenous FGF-2 in PTH responses, we examined PTH-induced OCL formation in bone marrow cultures from wild type and mice with a disruption of the Fgf2 gene. FGF-2-induced OCL formation was similar in marrow culture from both genotypes. In contrast, PTH-stimulated OCL formation in bone marrow cultures or co-cultures of osteoblast-spleen cells from Fgf2-/mice was significantly impaired. PTH increased RANKL mRNA expression in osteoblasts cultures from both genotypes. After 6 days of treatment, osteoprotegerin protein in cell supernatants was 40-fold higher in vehicle-treated and 30-fold higher in PTH-treated co-cultures of osteoblast and spleen cells from Fgf2-/mice compared with Fgf2+/+ mice. However, a neutralizing antibody to osteoprotegerin did not rescue reduced OCL formation in response to PTH. Injection of PTH caused hypercalcemia in Fgf2+/+ but not Fgf2-/mice. We conclude that PTH stimulates OCL formation and bone resorption in mice in part by endogenous FGF-2 synthesis by osteoblasts. Because RANKL- and interleukin-11-induced OCL formation was also reduced in bone marrow cultures from Fgf2-/mice, we further conclude that endogenous FGF-2 is necessary for maximal OCL formation by multiple bone resorbing factors. |
| doi_str_mv | 10.1074/jbc.M302113200 |
| format | Article |
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Douglas ; Hurley, Marja M.</creator><creatorcontrib>Okada, Yosuke ; Montero, Aldemar ; Zhang, Xuxia ; Sobue, Takanori ; Lorenzo, Joseph ; Doetschman, Thomas ; Coffin, J. Douglas ; Hurley, Marja M.</creatorcontrib><description>Fibroblast growth factor (FGF)-2 and parathyroid hormone (PTH) are potent inducers of osteoclast (OCL) formation, and PTH increases FGF-2 mRNA and protein expression in osteoblasts. To elucidate the role of endogenous FGF-2 in PTH responses, we examined PTH-induced OCL formation in bone marrow cultures from wild type and mice with a disruption of the Fgf2 gene. FGF-2-induced OCL formation was similar in marrow culture from both genotypes. In contrast, PTH-stimulated OCL formation in bone marrow cultures or co-cultures of osteoblast-spleen cells from Fgf2-/mice was significantly impaired. PTH increased RANKL mRNA expression in osteoblasts cultures from both genotypes. After 6 days of treatment, osteoprotegerin protein in cell supernatants was 40-fold higher in vehicle-treated and 30-fold higher in PTH-treated co-cultures of osteoblast and spleen cells from Fgf2-/mice compared with Fgf2+/+ mice. However, a neutralizing antibody to osteoprotegerin did not rescue reduced OCL formation in response to PTH. Injection of PTH caused hypercalcemia in Fgf2+/+ but not Fgf2-/mice. We conclude that PTH stimulates OCL formation and bone resorption in mice in part by endogenous FGF-2 synthesis by osteoblasts. Because RANKL- and interleukin-11-induced OCL formation was also reduced in bone marrow cultures from Fgf2-/mice, we further conclude that endogenous FGF-2 is necessary for maximal OCL formation by multiple bone resorbing factors.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M302113200</identifier><identifier>PMID: 12665515</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acid Phosphatase - analysis ; Animals ; Antibodies - pharmacology ; Bone Marrow Cells - cytology ; Carrier Proteins - genetics ; Carrier Proteins - pharmacology ; Cell Differentiation - drug effects ; Cells, Cultured ; Coculture Techniques ; Drug Interactions ; Fibroblast Growth Factor 2 - genetics ; Fibroblast Growth Factor 2 - pharmacology ; Giant Cells - cytology ; Glycoproteins - antagonists & inhibitors ; Glycoproteins - genetics ; Glycoproteins - immunology ; Interleukin-11 - pharmacology ; Isoenzymes - analysis ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - pharmacology ; Mice ; Mice, Transgenic ; Osteoclasts - cytology ; Osteoclasts - enzymology ; Osteoprotegerin ; Parathyroid Hormone - pharmacology ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B ; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - immunology ; Receptors, Tumor Necrosis Factor ; RNA, Messenger - analysis ; Skull - cytology ; Skull - drug effects ; Spleen - cytology ; Tartrate-Resistant Acid Phosphatase</subject><ispartof>The Journal of biological chemistry, 2003-06, Vol.278 (23), p.21258-21266</ispartof><rights>2003 © 2003 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-33b4bfb6131ecec190cd0892cef34aef30be0570d22be45a7499464b5df0e05a3</citedby><cites>FETCH-LOGICAL-c551t-33b4bfb6131ecec190cd0892cef34aef30be0570d22be45a7499464b5df0e05a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12665515$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Okada, Yosuke</creatorcontrib><creatorcontrib>Montero, Aldemar</creatorcontrib><creatorcontrib>Zhang, Xuxia</creatorcontrib><creatorcontrib>Sobue, Takanori</creatorcontrib><creatorcontrib>Lorenzo, Joseph</creatorcontrib><creatorcontrib>Doetschman, Thomas</creatorcontrib><creatorcontrib>Coffin, J. Douglas</creatorcontrib><creatorcontrib>Hurley, Marja M.</creatorcontrib><title>Impaired Osteoclast Formation in Bone Marrow Cultures of Fgf2 Null Mice in Response to Parathyroid Hormone</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Fibroblast growth factor (FGF)-2 and parathyroid hormone (PTH) are potent inducers of osteoclast (OCL) formation, and PTH increases FGF-2 mRNA and protein expression in osteoblasts. To elucidate the role of endogenous FGF-2 in PTH responses, we examined PTH-induced OCL formation in bone marrow cultures from wild type and mice with a disruption of the Fgf2 gene. FGF-2-induced OCL formation was similar in marrow culture from both genotypes. In contrast, PTH-stimulated OCL formation in bone marrow cultures or co-cultures of osteoblast-spleen cells from Fgf2-/mice was significantly impaired. PTH increased RANKL mRNA expression in osteoblasts cultures from both genotypes. After 6 days of treatment, osteoprotegerin protein in cell supernatants was 40-fold higher in vehicle-treated and 30-fold higher in PTH-treated co-cultures of osteoblast and spleen cells from Fgf2-/mice compared with Fgf2+/+ mice. However, a neutralizing antibody to osteoprotegerin did not rescue reduced OCL formation in response to PTH. Injection of PTH caused hypercalcemia in Fgf2+/+ but not Fgf2-/mice. We conclude that PTH stimulates OCL formation and bone resorption in mice in part by endogenous FGF-2 synthesis by osteoblasts. Because RANKL- and interleukin-11-induced OCL formation was also reduced in bone marrow cultures from Fgf2-/mice, we further conclude that endogenous FGF-2 is necessary for maximal OCL formation by multiple bone resorbing factors.</description><subject>Acid Phosphatase - analysis</subject><subject>Animals</subject><subject>Antibodies - pharmacology</subject><subject>Bone Marrow Cells - cytology</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - pharmacology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Drug Interactions</subject><subject>Fibroblast Growth Factor 2 - genetics</subject><subject>Fibroblast Growth Factor 2 - pharmacology</subject><subject>Giant Cells - cytology</subject><subject>Glycoproteins - antagonists & inhibitors</subject><subject>Glycoproteins - genetics</subject><subject>Glycoproteins - immunology</subject><subject>Interleukin-11 - pharmacology</subject><subject>Isoenzymes - analysis</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - pharmacology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Osteoclasts - cytology</subject><subject>Osteoclasts - enzymology</subject><subject>Osteoprotegerin</subject><subject>Parathyroid Hormone - pharmacology</subject><subject>RANK Ligand</subject><subject>Receptor Activator of Nuclear Factor-kappa B</subject><subject>Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - immunology</subject><subject>Receptors, Tumor Necrosis Factor</subject><subject>RNA, Messenger - analysis</subject><subject>Skull - cytology</subject><subject>Skull - drug effects</subject><subject>Spleen - cytology</subject><subject>Tartrate-Resistant Acid Phosphatase</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1P3DAQhq2KCrbAtUfkA-ot2_FHNskRVt2CxJaqolJvlu1MWK-SeLEdEP8eo12JU32YkexnXo0eE_KVwZxBJb9vjZ2vBXDGBAf4RGYMalGIkv07IjPI90XDy_qEfIlxC_nIhh2TE8YXi7Jk5Yxsb4eddgFbeh8TetvrmOjKh0En50fqRnrtR6RrHYJ_ocupT1PASH1HV48dp7-mvqdrZ_Gd_INx58eINHn6WwedNq_Bu5be5LgcckY-d7qPeH7op-Tv6sfD8qa4u_95u7y6K2xeKRVCGGk6s2CCoUXLGrAt1A232AmpcwGDUFbQcm5QlrqSTSMX0pRtB_lBi1PybZ-7C_5pwpjU4KLFvtcj-ikqVld1JQEyON-DNvgYA3ZqF9ygw6tioN7tqmxXfdjNAxeH5MkM2H7gB50ZuNwDG_e4eclalXHebnBQvKoVF4qz_BsZq_cYZg3PDoOK1uFosc0jNqnWu_-t8Ab5lJSR</recordid><startdate>20030606</startdate><enddate>20030606</enddate><creator>Okada, Yosuke</creator><creator>Montero, Aldemar</creator><creator>Zhang, Xuxia</creator><creator>Sobue, Takanori</creator><creator>Lorenzo, Joseph</creator><creator>Doetschman, Thomas</creator><creator>Coffin, J. Douglas</creator><creator>Hurley, Marja M.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20030606</creationdate><title>Impaired Osteoclast Formation in Bone Marrow Cultures of Fgf2 Null Mice in Response to Parathyroid Hormone</title><author>Okada, Yosuke ; Montero, Aldemar ; Zhang, Xuxia ; Sobue, Takanori ; Lorenzo, Joseph ; Doetschman, Thomas ; Coffin, J. Douglas ; Hurley, Marja M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-33b4bfb6131ecec190cd0892cef34aef30be0570d22be45a7499464b5df0e05a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Acid Phosphatase - analysis</topic><topic>Animals</topic><topic>Antibodies - pharmacology</topic><topic>Bone Marrow Cells - cytology</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - pharmacology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Drug Interactions</topic><topic>Fibroblast Growth Factor 2 - genetics</topic><topic>Fibroblast Growth Factor 2 - pharmacology</topic><topic>Giant Cells - cytology</topic><topic>Glycoproteins - antagonists & inhibitors</topic><topic>Glycoproteins - genetics</topic><topic>Glycoproteins - immunology</topic><topic>Interleukin-11 - pharmacology</topic><topic>Isoenzymes - analysis</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - pharmacology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Osteoclasts - cytology</topic><topic>Osteoclasts - enzymology</topic><topic>Osteoprotegerin</topic><topic>Parathyroid Hormone - pharmacology</topic><topic>RANK Ligand</topic><topic>Receptor Activator of Nuclear Factor-kappa B</topic><topic>Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - immunology</topic><topic>Receptors, Tumor Necrosis Factor</topic><topic>RNA, Messenger - analysis</topic><topic>Skull - cytology</topic><topic>Skull - drug effects</topic><topic>Spleen - cytology</topic><topic>Tartrate-Resistant Acid Phosphatase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Okada, Yosuke</creatorcontrib><creatorcontrib>Montero, Aldemar</creatorcontrib><creatorcontrib>Zhang, Xuxia</creatorcontrib><creatorcontrib>Sobue, Takanori</creatorcontrib><creatorcontrib>Lorenzo, Joseph</creatorcontrib><creatorcontrib>Doetschman, Thomas</creatorcontrib><creatorcontrib>Coffin, J. Douglas</creatorcontrib><creatorcontrib>Hurley, Marja M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Okada, Yosuke</au><au>Montero, Aldemar</au><au>Zhang, Xuxia</au><au>Sobue, Takanori</au><au>Lorenzo, Joseph</au><au>Doetschman, Thomas</au><au>Coffin, J. Douglas</au><au>Hurley, Marja M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired Osteoclast Formation in Bone Marrow Cultures of Fgf2 Null Mice in Response to Parathyroid Hormone</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2003-06-06</date><risdate>2003</risdate><volume>278</volume><issue>23</issue><spage>21258</spage><epage>21266</epage><pages>21258-21266</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Fibroblast growth factor (FGF)-2 and parathyroid hormone (PTH) are potent inducers of osteoclast (OCL) formation, and PTH increases FGF-2 mRNA and protein expression in osteoblasts. To elucidate the role of endogenous FGF-2 in PTH responses, we examined PTH-induced OCL formation in bone marrow cultures from wild type and mice with a disruption of the Fgf2 gene. FGF-2-induced OCL formation was similar in marrow culture from both genotypes. In contrast, PTH-stimulated OCL formation in bone marrow cultures or co-cultures of osteoblast-spleen cells from Fgf2-/mice was significantly impaired. PTH increased RANKL mRNA expression in osteoblasts cultures from both genotypes. After 6 days of treatment, osteoprotegerin protein in cell supernatants was 40-fold higher in vehicle-treated and 30-fold higher in PTH-treated co-cultures of osteoblast and spleen cells from Fgf2-/mice compared with Fgf2+/+ mice. However, a neutralizing antibody to osteoprotegerin did not rescue reduced OCL formation in response to PTH. Injection of PTH caused hypercalcemia in Fgf2+/+ but not Fgf2-/mice. We conclude that PTH stimulates OCL formation and bone resorption in mice in part by endogenous FGF-2 synthesis by osteoblasts. Because RANKL- and interleukin-11-induced OCL formation was also reduced in bone marrow cultures from Fgf2-/mice, we further conclude that endogenous FGF-2 is necessary for maximal OCL formation by multiple bone resorbing factors.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12665515</pmid><doi>10.1074/jbc.M302113200</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2003-06, Vol.278 (23), p.21258-21266 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acid Phosphatase - analysis Animals Antibodies - pharmacology Bone Marrow Cells - cytology Carrier Proteins - genetics Carrier Proteins - pharmacology Cell Differentiation - drug effects Cells, Cultured Coculture Techniques Drug Interactions Fibroblast Growth Factor 2 - genetics Fibroblast Growth Factor 2 - pharmacology Giant Cells - cytology Glycoproteins - antagonists & inhibitors Glycoproteins - genetics Glycoproteins - immunology Interleukin-11 - pharmacology Isoenzymes - analysis Membrane Glycoproteins - genetics Membrane Glycoproteins - pharmacology Mice Mice, Transgenic Osteoclasts - cytology Osteoclasts - enzymology Osteoprotegerin Parathyroid Hormone - pharmacology RANK Ligand Receptor Activator of Nuclear Factor-kappa B Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - immunology Receptors, Tumor Necrosis Factor RNA, Messenger - analysis Skull - cytology Skull - drug effects Spleen - cytology Tartrate-Resistant Acid Phosphatase |
| title | Impaired Osteoclast Formation in Bone Marrow Cultures of Fgf2 Null Mice in Response to Parathyroid Hormone |
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