Evidence map›Paper›PMID 36031590›Full record

ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2023

Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.

Junichi Kushioka, Masakazu Toya, Huaishuang Shen, Hirohito Hirata, Ning Zhang, Ejun Huang, Masanori Tsubosaka, Qi Gao, Victoria Teissier, Xueping Li and 2 more

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

Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. 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.

Junichi KushiokaDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.ORCID 0000-0002-0738-1569
Masakazu ToyaDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Huaishuang ShenDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Hirohito HirataDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Ning ZhangDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Ejun HuangDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Masanori TsubosakaDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Qi GaoDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Victoria TeissierDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Xueping LiDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
Takeshi UtsunomiyaDepartment of Orthopaedic Surgery, Kyusyu University, Fukuoka, Japan.
Stuart B GoodmanDepartment of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.ORCID 0000-0002-1919-3717
Stanford University · USKyushu University · JP

Funding

Wear Particle Disease and NF-kappa B SignalingR01AR063717 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2012 to 2021
$3.5M
Tissue Engineering Approaches for Improved Treatment of Early Stage Osteonecrosis of the HipR01AR072613 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B, YANG, YUNZHI · 2018 to 2022
$2.2M
Customized MSCs to Enhance Healing of Bone DefectsR01AR073145 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2018 to 2021
$1.4M
NIAMS NIH HHS R01 AR063717NIAMS NIH HHS R01 AR072613NIAMS NIH HHS R01 AR073145
6 · The paper itself

Abstract

The number of total joint replacements is increasing, especially in elderly patients, and so too are implant-related complications such as prosthesis loosening. Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF-ĸB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically-modified NF-ĸB sensing interleukin-4 over-secreting MSCs (IL4-MSCs) on chronic inflammation in aged mice. The model was generated by continuous infusion of contaminated polyethylene particles into the intramedullary space of the distal femur of aged mice (15-17 months old) for 6 weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast-like cells, increased alkaline phosphatase (ALP)-positive area, and increased M2/M1 macrophage ratio. Local injection of MSCs and IL4-MSCs significantly decreased osteoclast-like cells and increased the M2/M1 ratio, with a greater trend for IL4-MSCs than MSCs. MSCs significantly increased ALP-positive area and BMD values compared with the control. The IL4-MSCs demonstrated higher values for both ALP-positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4-MSCs on chronic inflammatory osteolysis in aged mice. The two MSC-based therapies were more effective than ODN in increasing the M2/M1 macrophage ratio, reducing bone resorption, and increasing bone formation. Specifically, MSCs were more effective in increasing bone formation, and IL4-MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle-associated inflammatory osteolysis after arthroplasty in the elderly.

Indexed as

Mesenchymal Stem CellsOsteolysisAnimalsInflammationInterleukin-4MiceNF-kappa BPolyethyleneInterleukin-4NF-kappa BPolyethyleneagingchronic inflammationmacrophagemesenchymal stem celloligodeoxynucleotideosteolysis

Identifiers

PMID36031590
PMCPMC9971358
OpenAlexW4293660109

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.