Vertebral Implantation of NELL-1 Enhances Bone Formation in an Osteoporotic Sheep Model

Background: Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor th...

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Veröffentlicht in:Tissue engineering. Part A 2016-06, Vol.22 (11-12), p.84-849
Hauptverfasser: James, Aaron W., Chiang, Michael, Asatrian, Greg, Shen, Jia, Goyal, Raghav, Chung, Choon G., Chang, Le, Shrestha, Swati, Turner, A. Simon, Seim, Howard B., Zhang, Xinli, Wu, Benjamin M., Ting, Kang, Soo, Chia
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container_end_page 849
container_issue 11-12
container_start_page 84
container_title Tissue engineering. Part A
container_volume 22
creator James, Aaron W.
Chiang, Michael
Asatrian, Greg
Shen, Jia
Goyal, Raghav
Chung, Choon G.
Chang, Le
Shrestha, Swati
Turner, A. Simon
Seim, Howard B.
Zhang, Xinli
Wu, Benjamin M.
Ting, Kang
Soo, Chia
description Background: Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor that possesses both pro-osteogenic and anti-osteoclastic properties, is a promising candidate for an alternative to current treatment modalities. This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep. Methods: Osteoporosis was induced through ovariectomy, dietary depletion of calcium and vitamin D, and steroid administration. After osteoporotic induction, lumbar vertebral body defect creation was performed. Sheep were randomly implanted with the control vehicle, comprised of hyaluronic acid (HA) with hydroxyapatite-coated β-tricalcium phosphate (β-TCP), or the treatment material of rhNELL-1 protein lyophilized onto β-TCP mixed with HA. Analysis of lumbar spine defect healing was performed by radiographic, histologic, and computer-simulated biomechanical testing. Results: rhNELL-1 treatment significantly increased lumbar spine bone formation, as determined by bone mineral density, % bone volume, and mean cortical width as assessed by micro-computed tomography. Histological analysis revealed a significant increase in bone area and osteoblast number and decrease in osteoclast number around the implant site. Computer-simulated biomechanical analysis of trabecular bone demonstrated that rhNELL-1-treatment resulted in a significantly more stress-resistant composition. Conclusion: Our findings suggest rhNELL-1-based vertebral implantation successfully improved cortical and cancellous bone regeneration in the lumbar spine of osteoporotic sheep. rhNELL-1-based bone graft substitutes represent a potential new local therapy.
doi_str_mv 10.1089/ten.tea.2015.0230
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Simon ; Seim, Howard B. ; Zhang, Xinli ; Wu, Benjamin M. ; Ting, Kang ; Soo, Chia</creator><creatorcontrib>James, Aaron W. ; Chiang, Michael ; Asatrian, Greg ; Shen, Jia ; Goyal, Raghav ; Chung, Choon G. ; Chang, Le ; Shrestha, Swati ; Turner, A. Simon ; Seim, Howard B. ; Zhang, Xinli ; Wu, Benjamin M. ; Ting, Kang ; Soo, Chia</creatorcontrib><description>Background: Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor that possesses both pro-osteogenic and anti-osteoclastic properties, is a promising candidate for an alternative to current treatment modalities. This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep. Methods: Osteoporosis was induced through ovariectomy, dietary depletion of calcium and vitamin D, and steroid administration. After osteoporotic induction, lumbar vertebral body defect creation was performed. Sheep were randomly implanted with the control vehicle, comprised of hyaluronic acid (HA) with hydroxyapatite-coated β-tricalcium phosphate (β-TCP), or the treatment material of rhNELL-1 protein lyophilized onto β-TCP mixed with HA. Analysis of lumbar spine defect healing was performed by radiographic, histologic, and computer-simulated biomechanical testing. Results: rhNELL-1 treatment significantly increased lumbar spine bone formation, as determined by bone mineral density, % bone volume, and mean cortical width as assessed by micro-computed tomography. Histological analysis revealed a significant increase in bone area and osteoblast number and decrease in osteoclast number around the implant site. Computer-simulated biomechanical analysis of trabecular bone demonstrated that rhNELL-1-treatment resulted in a significantly more stress-resistant composition. 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This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep. Methods: Osteoporosis was induced through ovariectomy, dietary depletion of calcium and vitamin D, and steroid administration. After osteoporotic induction, lumbar vertebral body defect creation was performed. Sheep were randomly implanted with the control vehicle, comprised of hyaluronic acid (HA) with hydroxyapatite-coated β-tricalcium phosphate (β-TCP), or the treatment material of rhNELL-1 protein lyophilized onto β-TCP mixed with HA. Analysis of lumbar spine defect healing was performed by radiographic, histologic, and computer-simulated biomechanical testing. Results: rhNELL-1 treatment significantly increased lumbar spine bone formation, as determined by bone mineral density, % bone volume, and mean cortical width as assessed by micro-computed tomography. Histological analysis revealed a significant increase in bone area and osteoblast number and decrease in osteoclast number around the implant site. Computer-simulated biomechanical analysis of trabecular bone demonstrated that rhNELL-1-treatment resulted in a significantly more stress-resistant composition. 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Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>James, Aaron W.</au><au>Chiang, Michael</au><au>Asatrian, Greg</au><au>Shen, Jia</au><au>Goyal, Raghav</au><au>Chung, Choon G.</au><au>Chang, Le</au><au>Shrestha, Swati</au><au>Turner, A. Simon</au><au>Seim, Howard B.</au><au>Zhang, Xinli</au><au>Wu, Benjamin M.</au><au>Ting, Kang</au><au>Soo, Chia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vertebral Implantation of NELL-1 Enhances Bone Formation in an Osteoporotic Sheep Model</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2016-06-01</date><risdate>2016</risdate><volume>22</volume><issue>11-12</issue><spage>84</spage><epage>849</epage><pages>84-849</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>Background: Vertebral compression fractures related to osteoporosis greatly afflict the aging population. One of the most commonly used therapy today is balloon kyphoplasty. However, this treatment is far from ideal and is associated with significant side effects. NELL-1, an osteoinductive factor that possesses both pro-osteogenic and anti-osteoclastic properties, is a promising candidate for an alternative to current treatment modalities. This study utilizes the pro-osteogenic properties of recombinant human NELL-1 (rhNELL-1) in lumbar spine vertebral defect model in osteoporotic sheep. Methods: Osteoporosis was induced through ovariectomy, dietary depletion of calcium and vitamin D, and steroid administration. After osteoporotic induction, lumbar vertebral body defect creation was performed. Sheep were randomly implanted with the control vehicle, comprised of hyaluronic acid (HA) with hydroxyapatite-coated β-tricalcium phosphate (β-TCP), or the treatment material of rhNELL-1 protein lyophilized onto β-TCP mixed with HA. Analysis of lumbar spine defect healing was performed by radiographic, histologic, and computer-simulated biomechanical testing. Results: rhNELL-1 treatment significantly increased lumbar spine bone formation, as determined by bone mineral density, % bone volume, and mean cortical width as assessed by micro-computed tomography. Histological analysis revealed a significant increase in bone area and osteoblast number and decrease in osteoclast number around the implant site. Computer-simulated biomechanical analysis of trabecular bone demonstrated that rhNELL-1-treatment resulted in a significantly more stress-resistant composition. Conclusion: Our findings suggest rhNELL-1-based vertebral implantation successfully improved cortical and cancellous bone regeneration in the lumbar spine of osteoporotic sheep. rhNELL-1-based bone graft substitutes represent a potential new local therapy.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>27113550</pmid><doi>10.1089/ten.tea.2015.0230</doi><tpages>766</tpages><oa>free_for_read</oa></addata></record>
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subjects Absorptiometry, Photon
Animals
Biomechanical Phenomena
Bone Density - drug effects
Bones
Cell Count
Disease Models, Animal
Finite Element Analysis
Growth factors
Humans
Implants, Experimental
Lumbar Vertebrae - diagnostic imaging
Lumbar Vertebrae - drug effects
Lumbar Vertebrae - pathology
Lumbar Vertebrae - physiopathology
Nerve Tissue Proteins - pharmacology
Original
Original Articles
Osteoblasts - drug effects
Osteoblasts - pathology
Osteoclasts - drug effects
Osteoclasts - pathology
Osteogenesis - drug effects
Osteoporosis
Osteoporosis - diagnostic imaging
Osteoporosis - pathology
Osteoporosis - physiopathology
Osteoporosis - therapy
Pneumoviridae
Sheep
Tissue engineering
Vertebrae
X-Ray Microtomography
title Vertebral Implantation of NELL-1 Enhances Bone Formation in an Osteoporotic Sheep Model
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