interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow
The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the...
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| Veröffentlicht in: | The Journal of cell biology 2004-12, Vol.167 (6), p.1113-1122 |
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| creator | Kuznetsov, Sergei A Riminucci, Mara Ziran, Navid Tsutsui, Takeo W Corsi, Alessandro Calvi, Laura Kronenberg, Henry M Schipani, Ernestina Robey, Pamela Gehron Bianco, Paolo |
| description | The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment. |
| doi_str_mv | 10.1083/jcb.200408079 |
| format | Article |
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The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.200408079</identifier><identifier>PMID: 15611335</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Adipocytes ; Animals ; Bone and Bones - cytology ; Bone and Bones - physiology ; Bone formation ; Bone marrow ; Bone Marrow - physiology ; Bone marrow cells ; Bones ; Cells, Cultured ; Female ; Gene Expression Profiling - methods ; Gene Expression Regulation, Developmental - physiology ; Hematopoiesis ; Hematopoiesis - genetics ; Hematopoiesis - physiology ; Histology ; Male ; Mice ; Mice, Transgenic ; Osteoblasts - physiology ; Osteogenesis - genetics ; Osteogenesis - physiology ; Parathyroid Hormone - genetics ; Parathyroid Hormone - metabolism ; Phenotype ; Receptor, Parathyroid Hormone, Type 1 - genetics ; Receptor, Parathyroid Hormone, Type 1 - metabolism ; Stem cells ; Stem Cells - cytology ; Stem Cells - physiology ; Stromal cells ; Transplantation</subject><ispartof>The Journal of cell biology, 2004-12, Vol.167 (6), p.1113-1122</ispartof><rights>Copyright 2004 The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27928,27929</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15611335$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuznetsov, Sergei A</creatorcontrib><creatorcontrib>Riminucci, Mara</creatorcontrib><creatorcontrib>Ziran, Navid</creatorcontrib><creatorcontrib>Tsutsui, Takeo W</creatorcontrib><creatorcontrib>Corsi, Alessandro</creatorcontrib><creatorcontrib>Calvi, Laura</creatorcontrib><creatorcontrib>Kronenberg, Henry M</creatorcontrib><creatorcontrib>Schipani, Ernestina</creatorcontrib><creatorcontrib>Robey, Pamela Gehron</creatorcontrib><creatorcontrib>Bianco, Paolo</creatorcontrib><title>interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.</description><subject>Adipocytes</subject><subject>Animals</subject><subject>Bone and Bones - cytology</subject><subject>Bone and Bones - physiology</subject><subject>Bone formation</subject><subject>Bone marrow</subject><subject>Bone Marrow - physiology</subject><subject>Bone marrow cells</subject><subject>Bones</subject><subject>Cells, Cultured</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation, Developmental - physiology</subject><subject>Hematopoiesis</subject><subject>Hematopoiesis - genetics</subject><subject>Hematopoiesis - physiology</subject><subject>Histology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Osteoblasts - physiology</subject><subject>Osteogenesis - genetics</subject><subject>Osteogenesis - physiology</subject><subject>Parathyroid Hormone - genetics</subject><subject>Parathyroid Hormone - metabolism</subject><subject>Phenotype</subject><subject>Receptor, Parathyroid Hormone, Type 1 - genetics</subject><subject>Receptor, Parathyroid Hormone, Type 1 - metabolism</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - physiology</subject><subject>Stromal cells</subject><subject>Transplantation</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EotOBJTsEXnWX1r9xzKISqoAiVaIS7TpyPDczHpI42E5hnpWXwekMha5YWLZ8Pp977jVCryg5paTiZ1vbnDJCBKmI0k_QgkpBiooK8hQtCGG00JLJI3Qc45ZkTAn-HB1RWVLKuVygX25IEMbO7LBvsY8J_BoGiC5iM6zwBnqT_OjdfPMOw88xQIzODzNtsPVDTC5Nyd1Bt8PGzgd8fXN5lle4xgEsjMkH7IYHb2exha6LeISQptBEnDaAISbTdC5uehjSbP6o8vy-8QPcZ8pi_AYdJNPh7Nkf7DIyG91jvQnB_3iBnrWmi_DysC_R7ccPNxeXxdWXT58v3l8VLRckFZwxpbgywsiSsUppKjizTdU2tOSCiYrphqgVMFuCXJnWSiB5dkI3VrOy1XyJzve-49T0sLK5g2C6egwu59jV3rj6sTK4Tb32dzWjipW5yBKdHAyC_z7lUdS9i3NXZgA_xbpUtFJC0v-CVCnNmBYZfPNvpIcsfz4-A6_3wDbm__mr5wnwimf57V5uja_NOrhY335lhHJCtJZSc_4bvp7I5w</recordid><startdate>20041220</startdate><enddate>20041220</enddate><creator>Kuznetsov, Sergei A</creator><creator>Riminucci, Mara</creator><creator>Ziran, Navid</creator><creator>Tsutsui, Takeo W</creator><creator>Corsi, Alessandro</creator><creator>Calvi, Laura</creator><creator>Kronenberg, Henry M</creator><creator>Schipani, Ernestina</creator><creator>Robey, Pamela Gehron</creator><creator>Bianco, Paolo</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20041220</creationdate><title>interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow</title><author>Kuznetsov, Sergei A ; Riminucci, Mara ; Ziran, Navid ; Tsutsui, Takeo W ; Corsi, Alessandro ; Calvi, Laura ; Kronenberg, Henry M ; Schipani, Ernestina ; Robey, Pamela Gehron ; Bianco, Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-f340t-3227737a4a56228791432cb8fb163424829b07de2c6e5dafc5e033549bc926f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adipocytes</topic><topic>Animals</topic><topic>Bone and Bones - cytology</topic><topic>Bone and Bones - physiology</topic><topic>Bone formation</topic><topic>Bone marrow</topic><topic>Bone Marrow - physiology</topic><topic>Bone marrow cells</topic><topic>Bones</topic><topic>Cells, Cultured</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation, Developmental - physiology</topic><topic>Hematopoiesis</topic><topic>Hematopoiesis - genetics</topic><topic>Hematopoiesis - physiology</topic><topic>Histology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Osteoblasts - physiology</topic><topic>Osteogenesis - genetics</topic><topic>Osteogenesis - physiology</topic><topic>Parathyroid Hormone - genetics</topic><topic>Parathyroid Hormone - metabolism</topic><topic>Phenotype</topic><topic>Receptor, Parathyroid Hormone, Type 1 - genetics</topic><topic>Receptor, Parathyroid Hormone, Type 1 - metabolism</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - physiology</topic><topic>Stromal cells</topic><topic>Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuznetsov, Sergei A</creatorcontrib><creatorcontrib>Riminucci, Mara</creatorcontrib><creatorcontrib>Ziran, Navid</creatorcontrib><creatorcontrib>Tsutsui, Takeo W</creatorcontrib><creatorcontrib>Corsi, Alessandro</creatorcontrib><creatorcontrib>Calvi, Laura</creatorcontrib><creatorcontrib>Kronenberg, Henry M</creatorcontrib><creatorcontrib>Schipani, Ernestina</creatorcontrib><creatorcontrib>Robey, Pamela Gehron</creatorcontrib><creatorcontrib>Bianco, Paolo</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuznetsov, Sergei A</au><au>Riminucci, Mara</au><au>Ziran, Navid</au><au>Tsutsui, Takeo W</au><au>Corsi, Alessandro</au><au>Calvi, Laura</au><au>Kronenberg, Henry M</au><au>Schipani, Ernestina</au><au>Robey, Pamela Gehron</au><au>Bianco, Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2004-12-20</date><risdate>2004</risdate><volume>167</volume><issue>6</issue><spage>1113</spage><epage>1122</epage><pages>1113-1122</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><abstract>The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>15611335</pmid><doi>10.1083/jcb.200408079</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Animals Bone and Bones - cytology Bone and Bones - physiology Bone formation Bone marrow Bone Marrow - physiology Bone marrow cells Bones Cells, Cultured Female Gene Expression Profiling - methods Gene Expression Regulation, Developmental - physiology Hematopoiesis Hematopoiesis - genetics Hematopoiesis - physiology Histology Male Mice Mice, Transgenic Osteoblasts - physiology Osteogenesis - genetics Osteogenesis - physiology Parathyroid Hormone - genetics Parathyroid Hormone - metabolism Phenotype Receptor, Parathyroid Hormone, Type 1 - genetics Receptor, Parathyroid Hormone, Type 1 - metabolism Stem cells Stem Cells - cytology Stem Cells - physiology Stromal cells Transplantation |
| title | interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow |
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