Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function

► We examine bone metabolism of engineered alendronate attached to Ti surfaces. ► Alendronate-immobilized Ti enhances activation of osteoblast differentiation. ► Alendronate-immobilized Ti inhibits osteoclast differentiation. ► Alendronate-immobilized Ti may be a bioactive implant with dual function...

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Veröffentlicht in:Biochemical and biophysical research communications 2011-09, Vol.413 (2), p.194-200
Hauptverfasser: Moon, Ho-Jin, Yun, Young-Pil, Han, Choong-Wan, Kim, Min Sung, Kim, Sung Eun, Bae, Min Soo, Kim, Gyu-Tae, Choi, Yong-Suk, Hwang, Eui-Hwan, Lee, Joon Woo, Lee, Jin-Moo, Lee, Chang-Hoon, Kim, Duck-Su, Kwon, Il Keun
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container_end_page 200
container_issue 2
container_start_page 194
container_title Biochemical and biophysical research communications
container_volume 413
creator Moon, Ho-Jin
Yun, Young-Pil
Han, Choong-Wan
Kim, Min Sung
Kim, Sung Eun
Bae, Min Soo
Kim, Gyu-Tae
Choi, Yong-Suk
Hwang, Eui-Hwan
Lee, Joon Woo
Lee, Jin-Moo
Lee, Chang-Hoon
Kim, Duck-Su
Kwon, Il Keun
description ► We examine bone metabolism of engineered alendronate attached to Ti surfaces. ► Alendronate-immobilized Ti enhances activation of osteoblast differentiation. ► Alendronate-immobilized Ti inhibits osteoclast differentiation. ► Alendronate-immobilized Ti may be a bioactive implant with dual functions. The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materials science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue. In this study, chemically active functional groups were introduced on the surface of Ti by a grafting reaction with heparin and then the Ti was functionalized by immobilizing alendronate onto the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation study, the alendronate-immobilized Ti substrates significantly enhanced alkaline phosphatase activity (ALP) and calcium content. Additionally, nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin, which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K, markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate-immobilized Ti were down-regulated. Our study suggests that alendronate-immobilized Ti may be a bioactive implant with dual functions to enhance osteoblast differentiation and to inhibit osteoclast differentiation simultaneously.
doi_str_mv 10.1016/j.bbrc.2011.08.057
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The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materials science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue. In this study, chemically active functional groups were introduced on the surface of Ti by a grafting reaction with heparin and then the Ti was functionalized by immobilizing alendronate onto the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation study, the alendronate-immobilized Ti substrates significantly enhanced alkaline phosphatase activity (ALP) and calcium content. Additionally, nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin, which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K, markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate-immobilized Ti were down-regulated. 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The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materials science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue. In this study, chemically active functional groups were introduced on the surface of Ti by a grafting reaction with heparin and then the Ti was functionalized by immobilizing alendronate onto the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation study, the alendronate-immobilized Ti substrates significantly enhanced alkaline phosphatase activity (ALP) and calcium content. Additionally, nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin, which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K, markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate-immobilized Ti were down-regulated. 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Yun, Young-Pil ; Han, Choong-Wan ; Kim, Min Sung ; Kim, Sung Eun ; Bae, Min Soo ; Kim, Gyu-Tae ; Choi, Yong-Suk ; Hwang, Eui-Hwan ; Lee, Joon Woo ; Lee, Jin-Moo ; Lee, Chang-Hoon ; Kim, Duck-Su ; Kwon, Il Keun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-81848afe36ca323b375cba849ca57a05839dc7fc0f0164181cb160500b7888803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Acid phosphatase (tartrate-resistant)</topic><topic>Alendronate</topic><topic>Alendronate - chemistry</topic><topic>Alendronate - pharmacology</topic><topic>Alendronic acid</topic><topic>ALKALINE PHOSPHATASE</topic><topic>Animals</topic><topic>Biocompatibility</topic><topic>Bisphosphonates</topic><topic>BONDING</topic><topic>Bone implants</topic><topic>BONE TISSUES</topic><topic>Cathepsin K</topic><topic>CATHEPSINS</topic><topic>CELL CULTURES</topic><topic>Cell Line</topic><topic>Coated Materials, Biocompatible - chemistry</topic><topic>Coated Materials, Biocompatible - pharmacology</topic><topic>Coatings</topic><topic>CONNECTIVE TISSUE CELLS</topic><topic>Dental restorative materials</topic><topic>Gene expression</topic><topic>GRAFTS</topic><topic>HEPARIN</topic><topic>Heparin - chemistry</topic><topic>Heparin - pharmacology</topic><topic>INHIBITION</topic><topic>LIGANDS</topic><topic>MECHANICAL PROPERTIES</topic><topic>MESSENGER-RNA</topic><topic>METABOLISM</topic><topic>Mice</topic><topic>Orthopedics</topic><topic>Osteoblast</topic><topic>Osteoblastogenesis</topic><topic>Osteoblasts - drug effects</topic><topic>Osteocalcin</topic><topic>Osteoclast</topic><topic>Osteoclastogenesis</topic><topic>Osteoclasts</topic><topic>Osteoclasts - drug effects</topic><topic>Osteogenesis</topic><topic>POLYMERASE CHAIN REACTION</topic><topic>RANK Ligand - pharmacology</topic><topic>SKELETON</topic><topic>Surface Properties</topic><topic>TITANIUM</topic><topic>Titanium - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moon, Ho-Jin</creatorcontrib><creatorcontrib>Yun, Young-Pil</creatorcontrib><creatorcontrib>Han, Choong-Wan</creatorcontrib><creatorcontrib>Kim, Min Sung</creatorcontrib><creatorcontrib>Kim, Sung Eun</creatorcontrib><creatorcontrib>Bae, Min Soo</creatorcontrib><creatorcontrib>Kim, Gyu-Tae</creatorcontrib><creatorcontrib>Choi, Yong-Suk</creatorcontrib><creatorcontrib>Hwang, Eui-Hwan</creatorcontrib><creatorcontrib>Lee, Joon Woo</creatorcontrib><creatorcontrib>Lee, Jin-Moo</creatorcontrib><creatorcontrib>Lee, Chang-Hoon</creatorcontrib><creatorcontrib>Kim, Duck-Su</creatorcontrib><creatorcontrib>Kwon, Il Keun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; 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The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materials science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue. In this study, chemically active functional groups were introduced on the surface of Ti by a grafting reaction with heparin and then the Ti was functionalized by immobilizing alendronate onto the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation study, the alendronate-immobilized Ti substrates significantly enhanced alkaline phosphatase activity (ALP) and calcium content. Additionally, nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin, which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K, markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate-immobilized Ti were down-regulated. Our study suggests that alendronate-immobilized Ti may be a bioactive implant with dual functions to enhance osteoblast differentiation and to inhibit osteoclast differentiation simultaneously.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21888898</pmid><doi>10.1016/j.bbrc.2011.08.057</doi><tpages>7</tpages></addata></record>
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subjects 60 APPLIED LIFE SCIENCES
Acid phosphatase (tartrate-resistant)
Alendronate
Alendronate - chemistry
Alendronate - pharmacology
Alendronic acid
ALKALINE PHOSPHATASE
Animals
Biocompatibility
Bisphosphonates
BONDING
Bone implants
BONE TISSUES
Cathepsin K
CATHEPSINS
CELL CULTURES
Cell Line
Coated Materials, Biocompatible - chemistry
Coated Materials, Biocompatible - pharmacology
Coatings
CONNECTIVE TISSUE CELLS
Dental restorative materials
Gene expression
GRAFTS
HEPARIN
Heparin - chemistry
Heparin - pharmacology
INHIBITION
LIGANDS
MECHANICAL PROPERTIES
MESSENGER-RNA
METABOLISM
Mice
Orthopedics
Osteoblast
Osteoblastogenesis
Osteoblasts - drug effects
Osteocalcin
Osteoclast
Osteoclastogenesis
Osteoclasts
Osteoclasts - drug effects
Osteogenesis
POLYMERASE CHAIN REACTION
RANK Ligand - pharmacology
SKELETON
Surface Properties
TITANIUM
Titanium - chemistry
title Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function
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