Evidence map›Paper›PMID 33581374›Full record

ArticleBone2021

The effects of high fat diet, bone healing, and BMP-2 treatment on endothelial cell growth and function.

Fazal Ur Rehman Bhatti, Ushashi C Dadwal, Conner R Valuch, Nikhil P Tewari, Olatundun D Awosanya, Caio de Andrade Staut, Seungyup Sun, Stephen K Mendenhall, Anthony J Perugini, Rohit U Nagaraj and 7 more

Open access · greenAbstract read
In one paragraph

Article in Bone, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Autophagy: regulating the seesaw of bone-fat balance.Frontiers in cell and developmental biology · 2025
    Review
  9. Thrombopoietic agents enhance bone healing in mice, rats, and pigs.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
    Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022
    Article
  17. Article
  18. Methodology, selection, and integration of fracture healing assessments in mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021
    Review
  19. Article
  20. 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

17 authors at 4 institutions in 1 country.

Fazal Ur Rehman BhattiDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA; Richard L. Roudebush VA Medical Center, IN, USA.
Ushashi C DadwalDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA; Richard L. Roudebush VA Medical Center, IN, USA.
Conner R ValuchDepartment of Biology, Indiana University Purdue University Indianapolis, IN, USA.
Nikhil P TewariDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Olatundun D AwosanyaDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Caio de Andrade StautDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Seungyup SunDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Stephen K MendenhallDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Anthony J PeruginiDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Rohit U NagarajDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Hanisha L BattinaDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Murad K NazzalDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Rachel J BlosserDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA; Richard L. Roudebush VA Medical Center, IN, USA.
Kevin A MaupinDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA.
Paul J ChildressDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA; Richard L. Roudebush VA Medical Center, IN, USA.
Jiliang LiDepartment of Biology, Indiana University Purdue University Indianapolis, IN, USA.
Melissa A KacenaDepartment of Orthopaedic Surgery, Indiana University School of Medicine, IN, USA; Richard L. Roudebush VA Medical Center, IN, USA. Electronic address: mkacena@iupui.edu.
Indiana University School of MedicineIndiana University · USIndiana University – Purdue University Indianapolis · USUniversity of Indianapolis · US

Funding

Translation CoreP30DK097512 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI AMBER L. MOSLEY · 2015 to 2026
$17.4M
Project-005U54DK106846 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Reuben Kapur, Karen Elizabeth Pollok · 2015 to 2026
$9.7M
BASIC SCIENCE STUDIES ON GENE THERAPY OF BLOOD DISEASEST32HL007910 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Roland W. Herzog, Reuben Kapur · 1999 to 2026
$7.6M
REGULATION OF HEMATOPOIETIC CELL PRODUCTIONT32DK007519 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI KAPLAN, MARK H · 1986 to 2020
$7.1M
Angiogenic Therapy: Novel Approaches to Enhance Bone Regeneration in Aging - LOADR01AG060621 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI KACENA, MELISSA A, LI, JILIANG · 2019 to 2023
$3.7M
Impact of TPO Treatment on Bone Healing and Angiogenesis in Type 2 DiabetesI01BX003751 · VA · RLR VA MEDICAL CENTER · PI KACENA, MELISSA A · 2017 to 2021
–
BLRD VA I01 BX003751NHLBI NIH HHS T32 HL007910NIA NIH HHS R01 AG060621NIDDK NIH HHS P30 DK097512NIDDK NIH HHS T32 DK007519NIDDK NIH HHS U54 DK106846RRD VA IK6 RX004809
6 · The paper itself

Abstract

Angiogenesis is a vital process during the regeneration of bone tissue. The aim of this study was to investigate angiogenesis at the fracture site as well as at distal locations from obesity-induced type 2 diabetic mice that were treated with bone morphogenetic protein-2 (BMP-2, local administration at the time of surgery) to heal a femoral critical sized defect (CSD) or saline as a control. Mice were fed a high fat diet (HFD) to induce a type 2 diabetic-like phenotype while low fat diet (LFD) animals served as controls. Endothelial cells (ECs) were isolated from the lungs (LECs) and bone marrow (BMECs) 3 weeks post-surgery, and the fractured femurs were also examined. Our studies demonstrate that local administration of BMP-2 at the fracture site in a CSD model results in complete bone healing within 3 weeks for all HFD mice and 66.7% of LFD mice, whereas those treated with saline remain unhealed. At the fracture site, vessel parameters and adipocyte numbers were significantly increased in BMP-2 treated femurs, irrespective of diet. At distal sites, LEC and BMEC proliferation was not altered by diet or BMP-2 treatment. HFD increased the tube formation ability of both LECs and BMECs. Interestingly, BMP-2 treatment at the time of surgery reduced tube formation in LECs and humeri BMECs. However, migration of BMECs from HFD mice treated with BMP-2 was increased compared to BMECs from HFD mice treated with saline. BMP-2 treatment significantly increased the expression of CD31, FLT-1, and ANGPT2 in LECs and BMECs in LFD mice, but reduced the expression of these same genes in HFD mice. To date, this is the first study that depicts the systemic influence of fracture surgery and local BMP-2 treatment on the proliferation and angiogenic potential of ECs derived from the bone marrow and lungs.

Indexed as

Diabetes Mellitus, ExperimentalFemoral FracturesAnimalsCell ProliferationDiet, High-FatEndothelial CellsMiceAngiogenesisBoneBone healingBone morphogenetic proteinBone regenerationEndothelial cellsFracture healingHigh fat dietType 2 diabetes

Identifiers

PMID33581374
PMCPMC8009863
OpenAlexW3128147828

What OpenQuestion holds

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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.