Evidence map›Paper›PMID 41981216›Full record

ArticlePharmaceutical research2026

The Versatile Role of GDF5 in Chondrogenic Progenitor Cell-mediated Cartilage Regeneration via a Hyaluronic Acid-fibrin IPN Hydrogel Platform.

Rui He, Venkateswaran Ganesh, Pornpoj Phruttiwanichakun, James A Martin, Dongrim Seol, Aliasger K Salem

Abstract read
In one paragraph

Article in Pharmaceutical research, 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. Article
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

6 authors.

Rui HePharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 180 S Grand Ave, Iowa City, IA, 52242, USA.
Venkateswaran GaneshDepartment of Orthopedics and Rehabilitation, Carver College of Medicine, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA.
Pornpoj PhruttiwanichakunPharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 180 S Grand Ave, Iowa City, IA, 52242, USA.
James A MartinPharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 180 S Grand Ave, Iowa City, IA, 52242, USA.
Dongrim SeolDepartment of Orthopedics and Rehabilitation, Carver College of Medicine, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA.
Aliasger K SalemPharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 180 S Grand Ave, Iowa City, IA, 52242, USA. aliasger-salem@uiowa.edu.

Funding

CST6-mRNA activated matrices for efficient bone regenerationR21DE031042 · NIDCR · UNIVERSITY OF IOWA · PI SALEM, ALIASGER K · 2022 to 2023
$425k
NIDCR NIH HHS R21 DE031042NIH HHS 5R21DE031042-02
6 · The paper itself

Abstract

objectiveFocal damage to articular cartilage incurred during joint injuries frequently progresses to post-traumatic osteoarthritis (PTOA) due to the limited intrinsic repair capacity of cartilage. Chondrogenic progenitor cells (CPCs) residing within the cartilage can contribute to repair if effectively recruited and activated. Early interventions that enhance CPC homing and their subsequent chondrogenesis offer a regenerative strategy to prevent PTOA progression, addressing the current lack of effective early clinical therapies. GDF5 stands out as a key protein involved in cartilage development, yet its potential to mobilize CPC-mediated regeneration remains underexplored.

methodsWe evaluated the effects of GDF5 on CPC migration, proliferation, chondrogenic differentiation, and anti-catabolic activity using in vitro CPC models. To assess CPC chemotaxis in a clinically relevant biomaterial context, GDF5 was incorporated into a hyaluronic acid/fibrin interpenetrating network (IPN) hydrogel and tested in an ex vivo cartilage defect model.

resultsGDF5 acted as a potent chemoattractant for CPCs, promoting their recruitment toward cartilage defects when delivered via a hyaluronic acid/fibrin IPN hydrogel in an ex vivo model. GDF5 also enhanced CPC proliferation, consistent with activation of a glycolysis-associated transcriptional program. In addition, GDF5 significantly upregulated chondrogenic markers, including SOX9, COL2a1, and ACAN, and elevated extracellular matrix components in CPCs, potentially through activation of the PI3K/AKT signaling pathway. Furthermore, GDF5 reduced expression of a key catabolic enzyme ADAMTS5, possibly through the WWP2/miR-140 axis.

conclusionThese findings highlight the versatile role of GDF5 on endogenous CPCs. When combined with a hydrogel platform, GDF5 may serve as an early therapeutic strategy to convert injured cartilage from a passive site of degeneration into one of active regeneration.

Indexed as

Cartilage, ArticularChondrogenesisGrowth Differentiation Factor 5RegenerationStem CellsAnimalsCell DifferentiationCell MovementCell ProliferationCells, CulturedChondrocytesFibrinHumansHyaluronic AcidHydrogelsFibrinGDF5 protein, humanGrowth Differentiation Factor 5Hyaluronic AcidHydrogelscell homingchondrogenic differentiationchondrogenic progenitor cellGDF5IPN hydrogel

Identifiers

PMID41981216
PMCPMC13545135

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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.