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Pharmacokinetics and osteogenic potential of PEGylated NELL-1 in vivo after systemic administration.
Kwak, Jin Hee; Zhang, Yulong; Park, Juyoung; Chen, Eric; Shen, Jia; Chawan, Chirag; Tanjaya, Justine; Lee, Soonchul; Zhang, Xinli; Wu, Benjamin M; Ting, Kang; Soo, Chia.
Affiliation
  • Kwak JH; Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: jkwak@dentistr
  • Zhang Y; Department of Bioengineering, University of California, Los Angeles, 5121K Engineering V, Los Angeles, CA 90095, USA; Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: leonzhang@ucla.edu.
  • Park J; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: orthosmile14@gmail.com.
  • Chen E; Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: Eric_Chen@post
  • Shen J; Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: shenj02@gmail.
  • Chawan C; Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: Chiragchouhan1
  • Tanjaya J; Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: justinetanjaya
  • Lee S; Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, South Korea. Electronic address: lsceline78@gmail.com.
  • Zhang X; Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: xzhang@dentist
  • Wu BM; Department of Bioengineering, University of California, Los Angeles, 5121K Engineering V, Los Angeles, CA 90095, USA; Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: benwu@ucla.edu.
  • Ting K; Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Orthopaedic Surgery
  • Soo C; Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angele
Biomaterials ; 57: 73-83, 2015 Jul.
Article in En | MEDLINE | ID: mdl-25913252
ABSTRACT
Osteoporosis is a skeletal disorder attributable to an imbalance in osteoblast and osteoclast activity. NELL-1, a secretory protein that promotes osteogenesis while suppressing osteoclastic activity, holds potential as an osteoporosis therapy. Recently, we demonstrated that PEGylation of NELL-1 significantly improves its thermostability while preserving its bioactivity in vitro. However, the effect of PEGylation on the pharmacokinetics and osteogenic potential of NELL-1 in vivo have yet to be investigated. The present study demonstrated that PEGylation of NELL-1 significantly increases the elimination half-life time of the protein from 5.5 h to 15.5 h while distributing more than 2-3 times the amount of protein to bone tissues (femur, tibia, vertebrae, calvaria) in vivo when compared to naked NELL-1. In addition, microCT and DXA analyses demonstrated that systemic NELL-PEG therapy administered every 4 or 7 days significantly increases not only femoral and lumbar BMD and percent bone volume, but also new bone formation throughout the overall skeleton after four weeks of treatment. Furthermore, immunohistochemistry revealed increased osteocalcin expression, while TRAP staining showed reduced osteoclast numbers in NELL-PEG groups. Our findings suggest that the PEGylation technique presents a viable and promising approach to further develop NELL-1 into an effective systemic therapeutic for the treatment of osteoporosis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteogenesis / Polyethylene Glycols / Calcium-Binding Proteins / Glycoproteins Limits: Animals Language: En Journal: Biomaterials Year: 2015 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteogenesis / Polyethylene Glycols / Calcium-Binding Proteins / Glycoproteins Limits: Animals Language: En Journal: Biomaterials Year: 2015 Document type: Article