Files and links (1)
Published, Version of Record (VoR) Open Access via Drexel Libraries Read and Publish Program 2026 Open CC BY-NC-ND V4.0
Journal article
Decorin promotes nascent proteoglycan retention in cartilage matrix by strengthening collagen II-aggrecan integration
Acta biomaterialia, Forthcoming
09 Jun 2026
PMID: 42263900
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
Cartilage extracellular matrix (ECM), a hydrated collagen II-aggrecan composite, undergoes dynamic turnover during both normal homeostasis and disease-associated remodeling. This study elucidates a crucial role for decorin in promoting the retention and stability of nascent aggrecan within this matrix. By applying bio-orthogonal click-labeling, we demonstrate that loss of decorin accelerates the release of nascent aggrecan under both physiological and inflammatory conditions, without affecting its preferential localization to the pericellular matrix. Conversely, supplementation with exogenous decorin mitigates inflammation-induced loss of nascent aggrecan, supporting its potential as a therapeutic target. At the molecular level, decorin exhibits strong binding affinity for aggrecan, and enhances aggrecan-aggrecan and aggrecan-collagen II interactions, reinforcing its direct role in integrating cartilage matrix constituents. Also, by binding to collagen II, decorin stiffens the collagen II fibril network, thereby strengthening the confinement effect that limits the diffusive loss of entrapped aggrecan. Notably, decorin does not alter chondrocyte transcriptomic profiles in vivo, emphasizing its primary role in maintaining matrix integrity through biophysical mechanisms rather than cell signaling. Together, these findings provide a mechanistic foundation for developing decorin-based biomaterials or gene therapies aimed at preserving or regenerating the cartilage matrix for improved outcomes in osteoarthritis. STATEMENT OF SIGNIFICANCE: Development of effective cartilage repair strategies is challenged by the limited understanding of molecular events that regulate the dynamic turnover and degenerative changes of cartilage extracellular matrix. This study shows that decorin, a small proteoglycan, promotes the retention and stability of nascent aggrecan within both normal and degenerative cartilage matrix by augmenting the integration between collagen II and aggrecan molecules and strengthening the collagen II fibril network. In turn, exogenous decorin mitigates the accelerated loss of nascent aggrecan instigated by inflammatory stimulation. Collectively, these findings establish decorin as a therapeutic target for preserving cartilage matrix integrity and improving osteoarthritis intervention.
Metrics
3 Record Views
Details
- Title
- Decorin promotes nascent proteoglycan retention in cartilage matrix by strengthening collagen II-aggrecan integration
- Creators
- Thomas Li - Drexel University, School of Biomedical Engineering, Science, and Health SystemsGabriela Canziani - Drexel University, Biochemistry and Molecular BiologyYuchen Liu - Drexel University, School of Biomedical Engineering, Science, and Health SystemsNeil Patel - Drexel University, School of Biomedical Engineering, Science, and Health SystemsBiao Han - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, United StatesMingyue Fan - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, United StatesAnnie Porter - University of DelawareBryan Kwok - Drexel University, School of Biomedical Engineering, Science, and Health SystemsChao Wang - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, United StatesQing Li - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, United StatesDavid E Birk - University of South FloridaRenato V Iozzo - Thomas Jefferson UniversityIrwin M Chaiken - Drexel University, Biochemistry and Molecular BiologyX Lucas Lu - University of DelawareRobert L Mauck - University of PennsylvaniaLin Han (Corresponding Author) - Drexel University, School of Biomedical Engineering, Science, and Health Systems
- Publication Details
- Acta biomaterialia, Forthcoming
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; School of Biomedical Engineering, Science, and Health Systems
- Other Identifier
- 991022185675704721