Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin

We investigated the effects of recombinant human BMP-2 (rhBMP-2) on differentiation of cells isolated from human bone, muscle, and skin. Cells isolated from bones of six patients (HBM-1 to HBM-6), muscle from five patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-3) were used. rhBMP-...

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Veröffentlicht in:Bone (New York, N.Y.) N.Y.), 1998-09, Vol.23 (3), p.223-231
Hauptverfasser: Kawasaki, K., Aihara, M., Honmo, J., Sakurai, S., Fujimaki, Y., Sakamoto, K., Fujimaki, E., Wozney, J.M., Yamaguchi, A.
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container_end_page 231
container_issue 3
container_start_page 223
container_title Bone (New York, N.Y.)
container_volume 23
creator Kawasaki, K.
Aihara, M.
Honmo, J.
Sakurai, S.
Fujimaki, Y.
Sakamoto, K.
Fujimaki, E.
Wozney, J.M.
Yamaguchi, A.
description We investigated the effects of recombinant human BMP-2 (rhBMP-2) on differentiation of cells isolated from human bone, muscle, and skin. Cells isolated from bones of six patients (HBM-1 to HBM-6), muscle from five patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-3) were used. rhBMP-2 had no effects on proliferation of two HBM cells, but had a stimulatory effect on three HM cell samples. rhBMP-2 stimulated both alkaline phosphatase (ALP) activity in all HBM cells and parathyroid hormone (PTH)-dependent cAMP production in three of the four HBM cell samples, although the magnitudes of these stimulatory effects differed among the cells tested. Although none of the HBM cells examined produced detectable amounts of osteocalcin in the absence of 1,25-(OH)2vitamin D3, they synthesized measurable amounts of osteocalcin in its presence. rhBMP-2 inhibited 1,25-(OH)2vitamin D3-dependent osteocalcin production in all of the HBM cell samples. Transplantation of HBM-6 cells with rhBMP-2 using diffusion chambers into the peritoneal cavity of athymic mice induced formation of cartilage and bone in the diffusion chambers, but neither cartilage nor bone was formed in chambers transplanted without rhBMP-2. rhBMP-2 also stimulated ALP activity in all of the HM and HF cell samples examined and PTH-dependent cAMP production in three of four HM cell samples. rhBMP-2 induced no osteocalcin production in any of the HM or HF cells in the presence of 1,25-(OH)2vitamin D3. rhBMP-2 markedly inhibited myotube formation by all of the HM cell samples. Transplantation of HM-4 cells with rhBMP-2, using diffusion chambers, into athymic mice induced ALP-positive cells in the chambers, but neither cartilage nor bone was observed. These results suggest that rhBMP-2 is a potent stimulator of osteoblast differentiation and bone formation in human cells.
doi_str_mv 10.1016/S8756-3282(98)00105-7
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Cells isolated from bones of six patients (HBM-1 to HBM-6), muscle from five patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-3) were used. rhBMP-2 had no effects on proliferation of two HBM cells, but had a stimulatory effect on three HM cell samples. rhBMP-2 stimulated both alkaline phosphatase (ALP) activity in all HBM cells and parathyroid hormone (PTH)-dependent cAMP production in three of the four HBM cell samples, although the magnitudes of these stimulatory effects differed among the cells tested. Although none of the HBM cells examined produced detectable amounts of osteocalcin in the absence of 1,25-(OH)2vitamin D3, they synthesized measurable amounts of osteocalcin in its presence. rhBMP-2 inhibited 1,25-(OH)2vitamin D3-dependent osteocalcin production in all of the HBM cell samples. Transplantation of HBM-6 cells with rhBMP-2 using diffusion chambers into the peritoneal cavity of athymic mice induced formation of cartilage and bone in the diffusion chambers, but neither cartilage nor bone was formed in chambers transplanted without rhBMP-2. rhBMP-2 also stimulated ALP activity in all of the HM and HF cell samples examined and PTH-dependent cAMP production in three of four HM cell samples. rhBMP-2 induced no osteocalcin production in any of the HM or HF cells in the presence of 1,25-(OH)2vitamin D3. rhBMP-2 markedly inhibited myotube formation by all of the HM cell samples. Transplantation of HM-4 cells with rhBMP-2, using diffusion chambers, into athymic mice induced ALP-positive cells in the chambers, but neither cartilage nor bone was observed. 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Psychology ; Human ; Humans ; Ilium - drug effects ; Mice ; Mice, Nude ; Muscle ; Muscles - drug effects ; Osteoblasts ; Osteocalcin - metabolism ; Parathyroid Hormone ; Recombinant Proteins - pharmacology ; Skeleton and joints ; Skin - drug effects ; Transforming Growth Factor beta - pharmacology ; Vertebrates: osteoarticular system, musculoskeletal system</subject><ispartof>Bone (New York, N.Y.), 1998-09, Vol.23 (3), p.223-231</ispartof><rights>1998 Elsevier Science Inc.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-e9fd536102c5fa8d8caccf2c6b04aca7f31e55f07474de82e35b6ed2aa259ff83</citedby><cites>FETCH-LOGICAL-c455t-e9fd536102c5fa8d8caccf2c6b04aca7f31e55f07474de82e35b6ed2aa259ff83</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(98)00105-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=2374286$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9737344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawasaki, K.</creatorcontrib><creatorcontrib>Aihara, M.</creatorcontrib><creatorcontrib>Honmo, J.</creatorcontrib><creatorcontrib>Sakurai, S.</creatorcontrib><creatorcontrib>Fujimaki, Y.</creatorcontrib><creatorcontrib>Sakamoto, K.</creatorcontrib><creatorcontrib>Fujimaki, E.</creatorcontrib><creatorcontrib>Wozney, J.M.</creatorcontrib><creatorcontrib>Yamaguchi, A.</creatorcontrib><title>Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin</title><title>Bone (New York, N.Y.)</title><addtitle>Bone</addtitle><description>We investigated the effects of recombinant human BMP-2 (rhBMP-2) on differentiation of cells isolated from human bone, muscle, and skin. Cells isolated from bones of six patients (HBM-1 to HBM-6), muscle from five patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-3) were used. rhBMP-2 had no effects on proliferation of two HBM cells, but had a stimulatory effect on three HM cell samples. rhBMP-2 stimulated both alkaline phosphatase (ALP) activity in all HBM cells and parathyroid hormone (PTH)-dependent cAMP production in three of the four HBM cell samples, although the magnitudes of these stimulatory effects differed among the cells tested. Although none of the HBM cells examined produced detectable amounts of osteocalcin in the absence of 1,25-(OH)2vitamin D3, they synthesized measurable amounts of osteocalcin in its presence. rhBMP-2 inhibited 1,25-(OH)2vitamin D3-dependent osteocalcin production in all of the HBM cell samples. Transplantation of HBM-6 cells with rhBMP-2 using diffusion chambers into the peritoneal cavity of athymic mice induced formation of cartilage and bone in the diffusion chambers, but neither cartilage nor bone was formed in chambers transplanted without rhBMP-2. rhBMP-2 also stimulated ALP activity in all of the HM and HF cell samples examined and PTH-dependent cAMP production in three of four HM cell samples. rhBMP-2 induced no osteocalcin production in any of the HM or HF cells in the presence of 1,25-(OH)2vitamin D3. rhBMP-2 markedly inhibited myotube formation by all of the HM cell samples. Transplantation of HM-4 cells with rhBMP-2, using diffusion chambers, into athymic mice induced ALP-positive cells in the chambers, but neither cartilage nor bone was observed. These results suggest that rhBMP-2 is a potent stimulator of osteoblast differentiation and bone formation in human cells.</description><subject>Alkaline Phosphatase - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone morphogenetic protein</subject><subject>Bone Morphogenetic Protein 2</subject><subject>Bone Morphogenetic Proteins - pharmacology</subject><subject>Calcitriol - pharmacology</subject><subject>Cell culture</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Transplantation</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP - metabolism</subject><subject>Diffusion Chambers, Culture</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Human</subject><subject>Humans</subject><subject>Ilium - drug effects</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Muscle</subject><subject>Muscles - drug effects</subject><subject>Osteoblasts</subject><subject>Osteocalcin - metabolism</subject><subject>Parathyroid Hormone</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Skeleton and joints</subject><subject>Skin - drug effects</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><issn>8756-3282</issn><issn>1873-2763</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuLFTEQhYMo452rP2EgCxEFW_PodNIrkWFGhQEX6jqkk4oT7U6uSVpw508398HFnasi1Dmnqr4gdEXJa0ro8OazkmLoOFPsxaheEkKJ6OQDtKFK8o7JgT9Em7PkMbos5TshhI-SXqCLUXLJ-36D_tx4D7YWnDzOYNMyhWhixffrYiKeUgS8pLy7T98gQg0W73KqEGLHcIrYhebOEGswNbR3C7EwzwWHkmZTwWGf0_JP2Cu8rMXOrZrocPkR4hP0yJu5wNNT3aKvtzdfrj90d5_ef7x-d9fZXojaweid4AMlzApvlFPWWOuZHSbSG2uk5xSE8ET2snegGHAxDeCYMUyM3iu-Rc-Pue2AnyuUqpdQ9suaCGktWvKxH0c1NKE4Cm1OpWTwepfDYvJvTYnek9cH8nqPVY9KH8g3-xZdnQas0wLu7Dqhbv1np74p1sw-m2hDOcsYlz07jH97lEGD8StA1sUGiBZcaP9TtUvhP4v8Bb1yopY</recordid><startdate>19980901</startdate><enddate>19980901</enddate><creator>Kawasaki, K.</creator><creator>Aihara, M.</creator><creator>Honmo, J.</creator><creator>Sakurai, S.</creator><creator>Fujimaki, Y.</creator><creator>Sakamoto, K.</creator><creator>Fujimaki, E.</creator><creator>Wozney, J.M.</creator><creator>Yamaguchi, A.</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>7X8</scope></search><sort><creationdate>19980901</creationdate><title>Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin</title><author>Kawasaki, K. ; Aihara, M. ; Honmo, J. ; Sakurai, S. ; Fujimaki, Y. ; Sakamoto, K. ; Fujimaki, E. ; Wozney, J.M. ; Yamaguchi, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-e9fd536102c5fa8d8caccf2c6b04aca7f31e55f07474de82e35b6ed2aa259ff83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Alkaline Phosphatase - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - cytology</topic><topic>Bone morphogenetic protein</topic><topic>Bone Morphogenetic Protein 2</topic><topic>Bone Morphogenetic Proteins - pharmacology</topic><topic>Calcitriol - pharmacology</topic><topic>Cell culture</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Transplantation</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP - metabolism</topic><topic>Diffusion Chambers, Culture</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Human</topic><topic>Humans</topic><topic>Ilium - drug effects</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Muscle</topic><topic>Muscles - drug effects</topic><topic>Osteoblasts</topic><topic>Osteocalcin - metabolism</topic><topic>Parathyroid Hormone</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Skeleton and joints</topic><topic>Skin - drug effects</topic><topic>Transforming Growth Factor beta - pharmacology</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawasaki, K.</creatorcontrib><creatorcontrib>Aihara, M.</creatorcontrib><creatorcontrib>Honmo, J.</creatorcontrib><creatorcontrib>Sakurai, S.</creatorcontrib><creatorcontrib>Fujimaki, Y.</creatorcontrib><creatorcontrib>Sakamoto, K.</creatorcontrib><creatorcontrib>Fujimaki, E.</creatorcontrib><creatorcontrib>Wozney, J.M.</creatorcontrib><creatorcontrib>Yamaguchi, A.</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>MEDLINE - Academic</collection><jtitle>Bone (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawasaki, K.</au><au>Aihara, M.</au><au>Honmo, J.</au><au>Sakurai, S.</au><au>Fujimaki, Y.</au><au>Sakamoto, K.</au><au>Fujimaki, E.</au><au>Wozney, J.M.</au><au>Yamaguchi, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin</atitle><jtitle>Bone (New York, N.Y.)</jtitle><addtitle>Bone</addtitle><date>1998-09-01</date><risdate>1998</risdate><volume>23</volume><issue>3</issue><spage>223</spage><epage>231</epage><pages>223-231</pages><issn>8756-3282</issn><eissn>1873-2763</eissn><abstract>We investigated the effects of recombinant human BMP-2 (rhBMP-2) on differentiation of cells isolated from human bone, muscle, and skin. Cells isolated from bones of six patients (HBM-1 to HBM-6), muscle from five patients (HM-1 to HM-5), and skin from three patients (HF-1 to HF-3) were used. rhBMP-2 had no effects on proliferation of two HBM cells, but had a stimulatory effect on three HM cell samples. rhBMP-2 stimulated both alkaline phosphatase (ALP) activity in all HBM cells and parathyroid hormone (PTH)-dependent cAMP production in three of the four HBM cell samples, although the magnitudes of these stimulatory effects differed among the cells tested. Although none of the HBM cells examined produced detectable amounts of osteocalcin in the absence of 1,25-(OH)2vitamin D3, they synthesized measurable amounts of osteocalcin in its presence. rhBMP-2 inhibited 1,25-(OH)2vitamin D3-dependent osteocalcin production in all of the HBM cell samples. Transplantation of HBM-6 cells with rhBMP-2 using diffusion chambers into the peritoneal cavity of athymic mice induced formation of cartilage and bone in the diffusion chambers, but neither cartilage nor bone was formed in chambers transplanted without rhBMP-2. rhBMP-2 also stimulated ALP activity in all of the HM and HF cell samples examined and PTH-dependent cAMP production in three of four HM cell samples. rhBMP-2 induced no osteocalcin production in any of the HM or HF cells in the presence of 1,25-(OH)2vitamin D3. rhBMP-2 markedly inhibited myotube formation by all of the HM cell samples. Transplantation of HM-4 cells with rhBMP-2, using diffusion chambers, into athymic mice induced ALP-positive cells in the chambers, but neither cartilage nor bone was observed. These results suggest that rhBMP-2 is a potent stimulator of osteoblast differentiation and bone formation in human cells.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9737344</pmid><doi>10.1016/S8756-3282(98)00105-7</doi><tpages>9</tpages></addata></record>
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ispartof Bone (New York, N.Y.), 1998-09, Vol.23 (3), p.223-231
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subjects Alkaline Phosphatase - metabolism
Animals
Biological and medical sciences
Bone Marrow Cells - cytology
Bone morphogenetic protein
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins - pharmacology
Calcitriol - pharmacology
Cell culture
Cell Differentiation - drug effects
Cell Transplantation
Cells, Cultured
Cyclic AMP - metabolism
Diffusion Chambers, Culture
Fundamental and applied biological sciences. Psychology
Human
Humans
Ilium - drug effects
Mice
Mice, Nude
Muscle
Muscles - drug effects
Osteoblasts
Osteocalcin - metabolism
Parathyroid Hormone
Recombinant Proteins - pharmacology
Skeleton and joints
Skin - drug effects
Transforming Growth Factor beta - pharmacology
Vertebrates: osteoarticular system, musculoskeletal system
title Effects of recombinant human bone morphogenetic protein-2 on differentiation of cells isolated from human bone, muscle, and skin
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