Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo
Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activit...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 1999-10, Vol.140 (10), p.4699-4705 |
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| description | Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo. |
| doi_str_mv | 10.1210/endo.140.10.7081 |
| format | Article |
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Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo.]]></description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/endo.140.10.7081</identifier><identifier>PMID: 10499528</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Alkaline phosphatase ; Alkaline Phosphatase - metabolism ; Animals ; Bone growth ; Cell proliferation ; Collagen (type I) ; Drug Combinations ; Femur - enzymology ; Growth factors ; Human performance ; Humans ; In vivo methods and tests ; Insulin ; Insulin-Like Growth Factor Binding Protein 5 - pharmacology ; Insulin-like growth factor I ; Insulin-Like Growth Factor I - analysis ; Insulin-Like Growth Factor I - pharmacology ; Insulin-like growth factor-binding protein 5 ; Insulin-like growth factors ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Osteoblasts ; Osteoblasts - drug effects ; Osteoblasts - physiology ; Osteocalcin ; Osteocalcin - blood ; Osteogenesis ; Osteogenesis - drug effects ; Osteogenesis - physiology ; Parameters ; Proteins ; Recombinant Proteins ; Species Specificity ; Tumor Cells, Cultured</subject><ispartof>Endocrinology (Philadelphia), 1999-10, Vol.140 (10), p.4699-4705</ispartof><rights>Copyright © 1999 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10499528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Richman, C</creatorcontrib><creatorcontrib>Baylink, D J</creatorcontrib><creatorcontrib>Lang, K</creatorcontrib><creatorcontrib>Dony, C</creatorcontrib><creatorcontrib>Mohan, S</creatorcontrib><title>Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description><![CDATA[Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo.]]></description><subject>Alkaline phosphatase</subject><subject>Alkaline Phosphatase - metabolism</subject><subject>Animals</subject><subject>Bone growth</subject><subject>Cell proliferation</subject><subject>Collagen (type I)</subject><subject>Drug Combinations</subject><subject>Femur - enzymology</subject><subject>Growth factors</subject><subject>Human performance</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Insulin</subject><subject>Insulin-Like Growth Factor Binding Protein 5 - pharmacology</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-Like Growth Factor I - analysis</subject><subject>Insulin-Like Growth Factor I - pharmacology</subject><subject>Insulin-like growth factor-binding protein 5</subject><subject>Insulin-like growth factors</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C3H</subject><subject>Osteoblasts</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - physiology</subject><subject>Osteocalcin</subject><subject>Osteocalcin - blood</subject><subject>Osteogenesis</subject><subject>Osteogenesis - drug effects</subject><subject>Osteogenesis - physiology</subject><subject>Parameters</subject><subject>Proteins</subject><subject>Recombinant Proteins</subject><subject>Species Specificity</subject><subject>Tumor Cells, Cultured</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLxDAUhYMozvjYu5KA4K5jbh5NuxTxBQOC6LqkTaoZ22RM0lH_vQHHjRtXlw8-DucehE6ALIACuTBO-wXwTGQhSQU7aA41F4UESXbRnBBghaRUztBBjKuMnHO2j2ZAeF0LWs3R56Pp_Nhap1zCr9OoHLYuToN1xWDfDH4J_iO94l51yYcie9q6F7wOPpmsCByTHadBJRNx653BvQ-jStY7vFZBjSaZEHMi3tgUPFZO_8DGH6G9Xg3RHG_vIXq-uX66uiuWD7f3V5fLYg0VpIILVlJgikDXal2Rrmy7WjOpGOtKqIUpq55S3mnNBDFAqSZVWee6xKhW9i07ROc_ubnz-2RiakYbOzMMyhk_xUYSWfGaiH9FkKzOs0EWz_6IKz8Fl59oGDAioKRCZut0a03taHSzDnZU4av5nZ59A5lMh88</recordid><startdate>199910</startdate><enddate>199910</enddate><creator>Richman, C</creator><creator>Baylink, D J</creator><creator>Lang, K</creator><creator>Dony, C</creator><creator>Mohan, S</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>199910</creationdate><title>Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo</title><author>Richman, C ; Baylink, D J ; Lang, K ; Dony, C ; Mohan, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p181t-4536213a01cbdd80c6bc9d37a33c6195e68f224cdd350e122d0869fac0eab7fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Alkaline phosphatase</topic><topic>Alkaline Phosphatase - metabolism</topic><topic>Animals</topic><topic>Bone growth</topic><topic>Cell proliferation</topic><topic>Collagen (type I)</topic><topic>Drug Combinations</topic><topic>Femur - enzymology</topic><topic>Growth factors</topic><topic>Human performance</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>Insulin</topic><topic>Insulin-Like Growth Factor Binding Protein 5 - pharmacology</topic><topic>Insulin-like growth factor I</topic><topic>Insulin-Like Growth Factor I - analysis</topic><topic>Insulin-Like Growth Factor I - pharmacology</topic><topic>Insulin-like growth factor-binding protein 5</topic><topic>Insulin-like growth factors</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C3H</topic><topic>Osteoblasts</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - physiology</topic><topic>Osteocalcin</topic><topic>Osteocalcin - blood</topic><topic>Osteogenesis</topic><topic>Osteogenesis - drug effects</topic><topic>Osteogenesis - physiology</topic><topic>Parameters</topic><topic>Proteins</topic><topic>Recombinant Proteins</topic><topic>Species Specificity</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Richman, C</creatorcontrib><creatorcontrib>Baylink, D J</creatorcontrib><creatorcontrib>Lang, K</creatorcontrib><creatorcontrib>Dony, C</creatorcontrib><creatorcontrib>Mohan, S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Richman, C</au><au>Baylink, D J</au><au>Lang, K</au><au>Dony, C</au><au>Mohan, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>1999-10</date><risdate>1999</risdate><volume>140</volume><issue>10</issue><spage>4699</spage><epage>4705</epage><pages>4699-4705</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract><![CDATA[Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo.]]></abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>10499528</pmid><doi>10.1210/endo.140.10.7081</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Alkaline phosphatase Alkaline Phosphatase - metabolism Animals Bone growth Cell proliferation Collagen (type I) Drug Combinations Femur - enzymology Growth factors Human performance Humans In vivo methods and tests Insulin Insulin-Like Growth Factor Binding Protein 5 - pharmacology Insulin-like growth factor I Insulin-Like Growth Factor I - analysis Insulin-Like Growth Factor I - pharmacology Insulin-like growth factor-binding protein 5 Insulin-like growth factors Mice Mice, Inbred BALB C Mice, Inbred C3H Osteoblasts Osteoblasts - drug effects Osteoblasts - physiology Osteocalcin Osteocalcin - blood Osteogenesis Osteogenesis - drug effects Osteogenesis - physiology Parameters Proteins Recombinant Proteins Species Specificity Tumor Cells, Cultured |
| title | Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo |
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