Evidence map›Paper›PMID 34268335›Full record

ReviewFrontiers in molecular biosciences2021

Regulation of ADAMTS Proteases.

Keron W J Rose, Nandaraj Taye, Stylianos Z Karoulias, Dirk Hubmacher

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in molecular biosciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

63 citing papers in PubMed, 95 citations in OpenAlex.

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  14. A novel compound heterozygous mutation inInternational journal of ophthalmology · 2026
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  20. Biological attributes of zinc-dependent endopeptidases in endothelial dysfunction associated with sepsis: a narrative review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review

3 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Keron W J RoseOrthopaedic Research Laboratories, Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Nandaraj TayeOrthopaedic Research Laboratories, Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Stylianos Z KarouliasOrthopaedic Research Laboratories, Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Dirk HubmacherOrthopaedic Research Laboratories, Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Icahn School of Medicine at Mount Sinai · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A disintegrin and metalloprotease with thrombospondin type I motifs (ADAMTS) proteases are secreted metalloproteinases that play key roles in the formation, homeostasis and remodeling of the extracellular matrix (ECM). The substrate spectrum of ADAMTS proteases can range from individual ECM proteins to entire families of ECM proteins, such as the hyalectans. ADAMTS-mediated substrate cleavage is required for the formation, remodeling and physiological adaptation of the ECM to the needs of individual tissues and organ systems. However, ADAMTS proteases can also be involved in the destruction of tissues, resulting in pathologies such as arthritis. Specifically, ADAMTS4 and ADAMTS5 contribute to irreparable cartilage erosion by degrading aggrecan, which is a major constituent of cartilage. Arthritic joint damage is a major contributor to musculoskeletal morbidity and the most frequent clinical indication for total joint arthroplasty. Due to the high sequence homology of ADAMTS proteases in their catalytically active site, it remains a formidable challenge to design ADAMTS isotype-specific inhibitors that selectively inhibit ADAMTS proteases responsible for tissue destruction without affecting the beneficial functions of other ADAMTS proteases. In vivo, proteolytic activity of ADAMTS proteases is regulated on the transcriptional and posttranslational level. Here, we review the current knowledge of mechanisms that regulate ADAMTS protease activity in tissues including factors that induce ADAMTS gene expression, consequences of posttranslational modifications such as furin processing, the role of endogenous inhibitors and pharmacological approaches to limit ADAMTS protease activity in tissues, which almost exclusively focus on inhibiting the aggrecanase activity of ADAMTS4 and ADAMTS5.

Indexed as

aggrecanalternative splicingarthritiscartilageextracellular matrixposttranslational modificationssmall molecule inhibitor

Identifiers

PMID34268335
PMCPMC8275829
OpenAlexW3176749688

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.