Evidence map›Paper›PMID 39940775›Full record

ArticleInternational journal of molecular sciences2025

LRP4 and Agrin Are Modulated by Cartilage Degeneration and Involved in β-Catenin Signaling in Human Articular Chondrocytes.

Shuichi Naniwa, Keiichiro Nishida, Aki Yoshida, Yoshihisa Nasu, Ryuichi Nakahara, Takashi Ohtsuki, Yoshifumi Hotta, Noriyuki Shimizu, Chinatsu Ichikawa, Deting Lin and 2 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Shuichi NaniwaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.ORCID 0009-0009-3587-4975
Keiichiro NishidaLocomotive Pain Center, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.ORCID 0000-0003-1260-586X
Aki YoshidaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.ORCID 0000-0002-4790-933X
Yoshihisa NasuLocomotive Pain Center, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Ryuichi NakaharaLocomotive Pain Center, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Takashi OhtsukiDepartment of Medical Technology, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Yoshifumi HottaDepartment of Orthopaedic Surgery, Sayo Central Hospital, 3529-3, Sayo-cho 679-5383, Japan.ORCID 0009-0000-7228-5496
Noriyuki ShimizuDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Chinatsu IchikawaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Deting LinDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Noriaki OtsukaDepartment of Orthopaedic Surgery, Section of Medicine, Division of Medicine, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Toshifumi OzakiDepartment of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.ORCID 0000-0003-1732-9307

Funding

Eisai (Japan) HHCS 20220626006
6 · The paper itself

Abstract

We investigated the roles of low-density lipoprotein receptor-related protein (LRP) 4 and its ligand Agrin in the pathophysiology of cartilage degeneration. Immunohistochemical analysis of human normal articular cartilage and cartilage tissues from patients with osteoarthritis (OA) obtained during surgery of the knee joint showed marked LRP4 expression in the early stages of OA, which then decreased with cartilage degeneration, whereas Agrin was consistently increased with cartilage degeneration. In normal human articular chondrocytes (NHACs), mild cyclic tensile strain (CTS) (0.5 Hz, 5% elongation, 2 h) increased the expression of LRP4 and aggrecan (ACAN), while intense CTS (0.5 Hz, 10% elongation, 6 h) increased the expression of Agrin without affecting LRP4 expression. Treatment with recombinant human (rh) Agrin downregulated the mRNA expression of LRP4 and ACAN, but upregulated the expression of LRP5/6, SRY-box transcription factor 9 (SOX9), Runt-related transcription factor 2 (RUNX2), and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4). Immunocytochemistry and Western blot analysis showed that rhAgrin treatment upregulated the expression of β-catenin and SOX9. Agrin knockdown by si

Indexed as

Agrinbeta CateninCartilage, ArticularChondrocytesLDL-Receptor Related ProteinsADAMTS4 ProteinAgedAggrecansCells, CulturedCore Binding Factor Alpha 1 SubunitFemaleHumansMaleMiddle AgedOsteoarthritisSignal TransductionADAMTS4 ProteinADAMTS4 protein, humanAggrecansAgrinbeta CateninCore Binding Factor Alpha 1 SubunitCTNNB1 protein, humanLDL-Receptor Related ProteinsLRP4 protein, humanRUNX2 protein, humanSOX9 protein, humanSOX9 Transcription FactorAgrinchondrocyteLRP4mechanical stressosteoarthritisSOX9β-catenin

Identifiers

PMID39940775
PMCPMC11817251

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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.