Evidence map›Paper›PMID 41547960›Full record

ArticleNPJ Regenerative medicine2026

Inhibition of CDK8 rescues impaired ischemic fracture healing.

Christina A Capobianco, Michelle J Song, Easton C Farrell, Alexander J Knights, Karen Kessell, Alexis Donneys, Jeanna T Schmanski, Luke R Schroeder, Mengqian Chen, Igor B Roninson and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ Regenerative medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. let-7c-5p promotes fracture healing by downregulating CDK8.Journal of orthopaedic surgery and research · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Christina A CapobiancoDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Michelle J SongDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Easton C FarrellDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Alexander J KnightsDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Karen KessellDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Alexis DonneysDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Jeanna T SchmanskiDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Luke R SchroederDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Mengqian ChenDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC, USA.
Igor B RoninsonDepartment of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC, USA.
Yadav WagleyDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.
Tristan MaerzDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA. maerzt@ethz.ch.
Kurt D HankensonDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA. kdhank@umich.edu.

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Precision Mapping of Knee Pain in Osteoarthritis: Understanding differences between pain with activity and restUC2AR082186 · NIAMS · RUSH UNIVERSITY MEDICAL CENTER · PI LOTZ, MARTIN K, MALFAIT, ANNE-MARIE · 2022 to 2025
$11.9M
Structure, Composition, & Histology Core - Core BP30AR069620 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KARL J JEPSEN · 2016 to 2026
$8.4M
Notch Signaling and Bone Fracture HealingR01AR055607 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Kurt David Hankenson, IVO Kalajzic · 2011 to 2026
$6.3M
Regulators of Ischemic Fracture HealingR01AR066028 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HANKENSON, KURT DAVID · 2015 to 2020
$2.7M
Sustained Biomaterial-mediated Inhibition of R-spondin 2 to Target Pathological Wnt Signaling in Post-Traumatic OsteoarthritisR01AR080035 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kurt David Hankenson · 2022 to 2026
$2.5M
CTSA Predoctoral T32 at the University of MichiganT32TR004371 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VICKI L ELLINGROD, MICHAEL Allan HOLINSTAT · 2023 to 2026
$2.2M
Fibrosis, inflammation, and osteophyte formation in post-traumatic osteoarthritisR00AR081894 · NIAMS · WASHINGTON UNIVERSITY · PI Alexander John Knights · 2025 to 2026
$477k
Bioerodible corticosteroid microparticle-drug as an intra-articular drug delivery system for osteoarthritis therapyR21AR080502 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ENIOLA-ADEFESO, OMOLOLA, MAERZ, TRISTAN · 2022 to 2023
$405k
Targeting Pathological Angiogenesis after Joint InjuryR21AR076487 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALFORD, ANDREA I, MAERZ, TRISTAN · 2021 to 2021
$378k
Autonomous RUNX2 suppression in genetically modified stem cell-derived chondrocytes as a disease modifying therapeutic for PTOAR21AR082016 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLEMAN, RHIMA, MAERZ, TRISTAN · 2023 to 2024
$356k
Fibrosis, inflammation, and osteophyte formation in post-traumatic osteoarthritisK99AR081894 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KNIGHTS, ALEXANDER JOHN · 2023 to 2024
$206k
NCATS NIH HHS T32 TR004371NCATS NIH HHS T32TR004371NCI NIH HHS P30 CA046592NIAMS NIH HHS F30 AR071201NIAMS NIH HHS F31 AR085942NIAMS NIH HHS F31AR085942NIAMS NIH HHS K99 AR081894NIAMS NIH HHS K99AR081894NIAMS NIH HHS P30 AR069620NIAMS NIH HHS R00 AR081894NIAMS NIH HHS R01 AR055607NIAMS NIH HHS R01 AR066028NIAMS NIH HHS R01AR066028NIAMS NIH HHS R01 AR080035NIAMS NIH HHS R01AR080035NIAMS NIH HHS R21 AR076487NIAMS NIH HHS R21 AR080502NIAMS NIH HHS R21 AR082016NIAMS NIH HHS UC2 AR082186
6 · The paper itself

Abstract

Annually, 10% of 15 million bone fractures in the US fail to heal, and fractures with compromised blood flow, i.e., ischemia, are five times more likely to become nonunions. While ischemia is known to impair healing, the cellular and molecular mechanisms underlying this deficiency are unclear. Wild-type mice with surgically-induced ischemia underwent tibia fractures, and single-cell RNA-sequencing was performed on calluses at days 4 and 7 post-fracture. We observed delayed chondrogenic differentiation and upregulation of Cyclin-Dependent Kinase 8 (Cdk8) by stromal progenitors and fibroblasts in the ischemic callus. Hypoxia induced CDK8 gene expression in human mesenchymal stromal cells (hMSC), and pharmacological CDK8 inhibition promoted hMSC chondrogenic and osteogenic potential. In vivo oral delivery of a CDK8 inhibitor enhanced callus chondrogenesis and mineralization, potentially improving ischemic fracture healing. Our results suggest that CDK8 impedes stromal cell differentiation and that its inhibition may be a clinically translatable approach to enhance ischemic fracture healing.

Identifiers

PMID41547960
PMCPMC12905151

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Registered trials

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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.