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

doi:10.1007/s11095-026-04079-3

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

Journal article

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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 and Aliasger K Salem

Pharmaceutical research

04/14/2026

DOI: 10.1007/s11095-026-04079-3

PMID: 41981216

Appears in UI Libraries Support Open Access

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Abstract

Focal 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. We 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. GDF5 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. These 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.

chondrogenic differentiation

chondrogenic progenitor cell

GDF5

cell homing

IPN hydrogel

UIOWA OA Agreement

Details

Title: Subtitle: The Versatile Role of GDF5 in Chondrogenic Progenitor Cell-mediated Cartilage Regeneration via a Hyaluronic Acid-fibrin IPN Hydrogel Platform
Creators: Rui He - University of Iowa
Venkateswaran Ganesh - University of Iowa
Pornpoj Phruttiwanichakun - University of Iowa
James A Martin - University of Iowa
Dongrim Seol - University of Iowa
Aliasger K Salem - University of Iowa
Resource Type: Journal article
Publication Details: Pharmaceutical research
DOI: 10.1007/s11095-026-04079-3
PMID: 41981216
NLM abbreviation: Pharm Res
ISSN: 0724-8741
eISSN: 1573-904X
Publisher: Springer Nature
Grant note: 5R21DE031042-02 / NIH HHS
Language: English
Electronic publication date: 04/14/2026
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Research Administration; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9985153532002771

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