Evidence map›Paper›PMID 37723136›Full record

ArticleNPJ microgravity2023

Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice.

Pin Ha, Jin Hee Kwak, Yulong Zhang, Jiayu Shi, Luan Tran, Timothy Pan Liu, Hsin-Chuan Pan, Samantha Lee, Jong Kil Kim, Eric Chen and 9 more

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

Article in NPJ microgravity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. NELL-1: role and mechanisms in disease pathogenesis and development.Frontiers in cell and developmental biology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
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

19 authors at 5 institutions in 1 country.

Pin Ha *Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-8934-0874
Jin Hee Kwak *Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90089, USA.
Yulong Zhang *Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jiayu ShiSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Luan TranDivision of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Timothy Pan LiuDivision of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Hsin-Chuan PanSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Samantha LeeDivision of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jong Kil KimDivision of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Eric ChenSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Yasaman Shirazi-FardSpace Biosciences Division, NASA Ames Research Center, Moffett Field, CA, 94035, USA.ORCID http://orcid.org/0000-0002-6520-3824
Louis S StodieckBioServe Space Technologies and Aerospace Engineering Sciences, University of Colorado, Boulder, CO, 80303, USA.
Andy LinOffice of Advanced Research Computing, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Zhong ZhengDivision of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-4905-3563
Stella Nuo DongSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Xinli ZhangSchool of Dentistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Benjamin M WuDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA. bwu@forsyth.org.ORCID http://orcid.org/0000-0001-5236-8534
Kang TingForsyth Institute, Cambridge, MA, 02142, USA. erickangting@gmail.com.
Chia SooDivision of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA. bsoo@ucla.edu.ORCID http://orcid.org/0000-0003-2444-5963
University of California, Los Angeles · USAmes Research Center · USForsyth Technical Community College · USUniversity of Colorado Boulder · USUniversity of Southern California · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Dual roles of Nell-1 in craniofacial bones and brain through interaction with Cntnap4R01DE029353 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SOO, CHIA, ZHANG, XINLI · 2020 to 2024
$2.5M
NELL-1's functional role in cartilage regenerationR01AR068835 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EASLEY, JEREMIAH, SOO, CHIA · 2015 to 2019
$2.2M
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
Novel systemic PEGylated NELL-1 therapy for craniofacial osteoporosisK08DE026805 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KWAK, JIN HEE · 2017 to 2020
$633k
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NIAMS NIH HHS R01 AR061399NIAMS NIH HHS R01 AR066782NIAMS NIH HHS R01 AR068835NIDCR NIH HHS K08 DE026805NIDCR NIH HHS R01 DE029353
6 · The paper itself

Abstract

Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1's osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).

Identifiers

PMID37723136
PMCPMC10507033
OpenAlexW4386833420

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.