Evidence map›Paper›PMID 35372645›Full record

ArticleBone reports2022

Effects of oral losartan administration on homeostasis of articular cartilage and bone in a rabbit model.

Zhenhan Deng, Xueqin Gao, Hajime Utsunomiya, Justin W Arner, Joseph J Ruzbarsky, Matthieu Huard, Sudheer Ravuri, Marc J Philippon, Johnny Huard

Open access · goldAbstract read
In one paragraph

Article in Bone reports, 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
0.7field-weighted citation impact, top 31% 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, 5 citations in OpenAlex.

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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 2 institutions in 1 country.

Zhenhan DengDepartment of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Xueqin GaoDepartment of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Hajime UtsunomiyaSteadman Philippon Research Institute, Vail, CO, USA.
Justin W ArnerSteadman Philippon Research Institute, Vail, CO, USA.
Joseph J RuzbarskySteadman Philippon Research Institute, Vail, CO, USA.
Matthieu HuardSteadman Philippon Research Institute, Vail, CO, USA.
Sudheer RavuriSteadman Philippon Research Institute, Vail, CO, USA.
Marc J PhilipponSteadman Philippon Research Institute, Vail, CO, USA.
Johnny HuardDepartment of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Steadman Philippon Research Institute · USThe University of Texas Health Science Center at Houston · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background and aims: Previous work has shown that oral losartan can enhance microfracture-mediated cartilage repair in a rabbit osteochondral defect injury model. In this study, we aimed to determine whether oral losartan would have a detrimental effect on articular cartilage and bone homeostasis in the uninjured sides. Methods: New Zealand rabbits were divided into 4 groups including normal uninjured (Normal), contralateral uninjured side of osteochondral defect (Defect), osteochondral defect plus microfracture (Microfracture) and osteochondral defect plus microfracture and losartan oral administration (10 mg/kg/day) (Losartan). Rabbits underwent different surgeries and treatment and were sacrificed at 12 weeks. Both side of the normal group and uninjured side of treatment groups tibias were harvested for Micro-CT and histological analysis for cartilage and bone including H&E staining, Herovici's staining (bone and cartilage) Alcian blue and Safranin O staining (cartilage) as well as immunohistochemistry of losartan related signaling pathways molecules for both cartilage and bone. Results: Our results showed losartan oral treatment at 10 mg/kg/day slightly increase Alcian blue positive matrix as well as decrease collagen type 3 in articular cartilage while having no significant effect on articular cartilage structure, cellularity, and other matrix. Losartan treatment also did not affect angiotensin receptor type 1 (AGTR1), angiotensin receptor type 2 (AGTR2) and phosphorylated transforming factor β1 activated kinase 1 (pTAK1) expression level and pattern in the articular cartilage. Furthermore, losartan treatment did not affect microarchitecture of normal cancellous bone and cortical bone of tibias compared to normal and other groups. Losartan treatment slightly increased osteocalcin positive osteoblasts on the surface of cancellous bone and did not affect bone matrix collagen type 1 content and did not change AGTR1, AGTR2 and pTAK1 signal molecule expression. Conclusion: Oral losartan used as a microfracture augmentation therapeutic does not have significant effect on uninjured articular cartilage and bone based on our preclinical rabbit model. These results provided further evidence that the current regimen of using losartan as a microfracture augmentation therapeutic is safe with respect to bone and cartilage homeostasis and support clinical trials for its application in human cartilage repair.

Indexed as

2D, 2 dimension3D, 3 dimensionAGTR1, angiotensin II receptor type 1AGTR2, angiotensin II receptor type 2AngII, angiotensin IIARRIVE, Animal Research: Reporting of In Vivo ExperimentsArticular cartilageAT1, angiotensin type 1BoneBV, bone volumeBV/TV, bone volume/total volumeCol1, collagen type ICol3, collagen type 3Ct.Th, cortical thicknessDMM, destabilization of the medial meniscusEDTA, ethylenediaminetetraacetic acid disodium dihydrateH&E, Hematoxylin &eosinHomeostasisLosartanMicro-CT, Micro-computer tomographyMicrofractureOCN, osteocalcinpSMAD2/3, phosphorylated mothers against decapentaplegic homologpTAK1, phosphorylated transforming growth factor β (TGF-β)-activated kinase 1RA, rheumatoid arthritisRAS, rennin-angiotensin systemSMAD7, mothers against decapentaplegic homolog 7Tb.N, trabecular numberTb.Sp, trabecular seperationTb.Th, trabecular thickness

Identifiers

PMID35372645
PMCPMC8971351
OpenAlexW4220653187

What OpenQuestion holds

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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.