Evidence map›Paper›PMID 25913252›Full record

ArticleBiomaterials2015

Pharmacokinetics and osteogenic potential of PEGylated NELL-1 in vivo after systemic administration.

Jin Hee Kwak, Yulong Zhang, Juyoung Park, Eric Chen, Jia Shen, Chirag Chawan, Justine Tanjaya, Soonchul Lee, Xinli Zhang, Benjamin M Wu and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.7field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. NELL-1: role and mechanisms in disease pathogenesis and development.Frontiers in cell and developmental biology · 2026
    Review
  3. Article
  4. Review
  5. Role of NEL‑like molecule‑1 in osteogenesis/chondrogenesis (Review).International journal of molecular medicine · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Jin Hee KwakDivision 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@dentistry.ucla.edu.
Yulong ZhangDepartment 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.
Juyoung ParkDepartment of Craniofacial Research Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: orthosmile14@gmail.com.
Eric ChenDivision 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.harvard.edu.
Jia ShenDivision 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.com.
Chirag ChawanDivision 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: Chiragchouhan13@gmail.com.
Justine TanjayaDivision 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@gmail.com.
Soonchul LeeDepartment of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, South Korea. Electronic address: lsceline78@gmail.com.
Xinli ZhangDivision 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@dentistry.ucla.edu.
Benjamin M WuDepartment 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.
Kang TingDivision 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 and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: kting@dentistry.ucla.edu.
Chia SooDepartment 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 Angeles, CA 90095, USA. Electronic address: bsoo@ucla.edu.
University of California, Los Angeles · USCHA University Bundang Medical Center · KR

Funding

NELL-1 Systemic Therapy for OsteoporosisR01AR066782 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EASLEY, JEREMIAH, TING, KANG · 2014 to 2018
$2.0M
Wnt and PPARy Signaling in Nell-1 and BMP2 Mediated Bone RegenerationR01AR061399 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SOO, CHIA · 2012 to 2016
$1.7M
NIAMS NIH HHS R01 AR061399NIAMS NIH HHS R01 AR061399-01A1NIAMS NIH HHS R01 AR066782NIAMS NIH HHS R01AR 066782-01
6 · The paper itself

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.

Indexed as

OsteogenesisAnimalsBone DensityBone Marrow CellsCalcium-Binding ProteinsCell DifferentiationCells, CulturedGlycoproteinsMiceOsteoclastsPolyethylene GlycolsStromal CellsCalcium-Binding ProteinsGlycoproteinsNell1 protein, mousePolyethylene GlycolsNELL-1OsteogenesisOsteoporosisPEGylationPharmacokinetics

Identifiers

PMID25913252
PMCPMC4426150
OpenAlexW2023128938

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.