Evidence map›Paper›PMID 35816198›Full record

ArticleEuropean spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society2022

TAK-242 treatment and its effect on mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice.

Mitchel C Whittal, Sarah J Poynter, Kayla Samms, K Josh Briar, Sabrina I Sinopoli, Magali Millecamps, Laura S Stone, Stephanie J DeWitte-Orr, Diane E Gregory

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In one paragraph

Article in European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

9 authors at 3 institutions in 2 countries.

Mitchel C WhittalDepartment of Kinesiology and Physical Education, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON, N2L 3C5, Canada.
Sarah J PoynterDepartment of Health Sciences, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON, N2L 3C5, Canada.
Kayla SammsDepartment of Health Sciences, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON, N2L 3C5, Canada.
K Josh BriarDepartment of Kinesiology and Physical Education, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON, N2L 3C5, Canada.
Sabrina I SinopoliDepartment of Kinesiology and Physical Education, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON, N2L 3C5, Canada.
Magali MillecampsMcGill University, 845 Sherbrooke Street West, Montréal, QC, H3A 0G4, Canada.
Laura S StoneMcGill University, 845 Sherbrooke Street West, Montréal, QC, H3A 0G4, Canada.
Stephanie J DeWitte-OrrDepartment of Health Sciences, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON, N2L 3C5, Canada.
Diane E GregoryDepartment of Kinesiology and Physical Education, Wilfrid Laurier University, 75 University Ave W, Waterloo, ON, N2L 3C5, Canada. dgregory@wlu.ca.ORCID 0000-0002-8295-7425
Wilfrid Laurier University · CAMcGill University · CAUniversity of Minnesota · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIntervertebral disc (IVD) degeneration is accompanied by mechanical and gene expression changes to IVDs. SPARC-null mice display accelerated IVD degeneration, and treatment with (toll-like receptor 4 (TLR4) inhibitor) TAK-242 decreases proinflammatory cytokines and pain. This study examined if chronic TAK-242 treatment impacts mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice.

methodsMale and female SPARC-null and WT mice aged 7-9 months were given intraperitoneal injections with TAK-242 or an equivalent saline vehicle for 8 weeks (3x/per week, M-W-F). L2-L5 spinal segments were tested in cyclic axial tension and compression. Gene expression analysis (RT-qPCR) was performed on male IVD tissues using Qiagen RT2 PCR arrays.

resultsSPARC-null mice had decreased NZ length (p = 0.001) and increased NZ stiffness (p < 0.001) compared to WT mice. NZ length was not impacted by TAK-242 treatment (p = 0.967) despite increased hysteresis energy (p = 0.024). Tensile stiffness was greater in SPARC-null mice (p = 0.018), and compressive (p < 0.001) stiffness was reduced from TAK-242 treatment in WT but not SPARC-null mice (p = 0.391). Gene expression analysis found upregulation of 13 ECM and 5 inflammatory genes in SPARC-null mice, and downregulation of 2 inflammatory genes after TAK-242 treatment.

conclusionsTAK-242 had limited impacts on SPARC-null mechanical properties and did not attenuate NZ mechanical changes associated with IVD degeneration. Expression analysis revealed an increase in ECM and inflammatory gene expression in SPARCnull mice with a reduction in inflammatory expression due to TAK-242 treatment. This study provides insight into the role of TLR4 in SPARC-null mediated IVD degeneration.

Indexed as

Intervertebral DiscIntervertebral Disc DegenerationAnimalsCytokinesFemaleGene ExpressionMaleMiceMice, KnockoutSulfonamidesToll-Like Receptor 4Cytokinesethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylateSulfonamidesToll-Like Receptor 4Axial loadingDegenerationGene expressionInflammationIntervertebral discTAK- 242

Identifiers

PMID35816198
OpenAlexW4285036089

What OpenQuestion holds

Textmetadata
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.