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Record W2897908104 · doi:10.1242/dmm.033662

17-DMAG regulates p21 expression to induce chondrogenesis <i>in vitro</i> and <i>in vivo</i>

2018· article· en· W2897908104 on OpenAlexafffund
Karri L. Bertram, Nadia Narendran, Pankaj Tailor, C.L. Jablonski, Catherine Léonard, Edward B. Irvine, Ricarda Hess, Anand O. Masson, Saleem Abubacker, Kristina D. Rinker, Jeff Biernaskie, Robin M. Yates, Paul Salo, Aru Narendran, Roman Krawetz

Bibliographic record

VenueDisease Models & Mechanisms · 2018
Typearticle
Languageen
FieldMedicine
TopicOsteoarthritis Treatment and Mechanisms
Canadian institutionsAlberta Children's HospitalAlberta Bone and Joint Health InstituteUniversity of Calgary
FundersCumming School of Medicine, University of CalgaryCanadian Institutes of Health ResearchAlberta Innovates - Health SolutionsStem Cell NetworkUniversity of Calgary
KeywordsChondrogenesisCartilageIn vivoMesenchymal stem cellIn vitroCell biologyOsteoarthritisRegeneration (biology)BiologyCancer researchKnockout mousePhenotypePopulationImmunologyPathologyMedicineAnatomyReceptorGeneticsGene

Abstract

fetched live from OpenAlex

ABSTRACT Cartilage degeneration after injury affects a significant percentage of the population, including those that will go on to develop osteoarthritis (OA). Like humans, most mammals, including mice, are incapable of regenerating injured cartilage. Interestingly, it has previously been shown that p21 (Cdkn1a) knockout (p21−/−) mice demonstrate auricular (ear) cartilage regeneration. However, the loss of p21 expression is highly correlated with the development of numerous types of cancer and autoimmune diseases, limiting the therapeutic translation of these findings. Therefore, in this study, we employed a screening approach to identify an inhibitor (17-DMAG) that negatively regulates the expression of p21. We also validated that this compound can induce chondrogenesis in vitro (in adult mesenchymal stem cells) and in vivo (auricular cartilage injury model). Furthermore, our results suggest that 17-DMAG can induce the proliferation of terminally differentiated chondrocytes (in vitro and in vivo), while maintaining their chondrogenic phenotype. This study provides new insights into the regulation of chondrogenesis that might ultimately lead to new therapies for cartilage injury and/or OA.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.018
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.246
Teacher spread0.231 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations19
Published2018
Admission routes2
Has abstractyes

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