ArticleThe Journal of biological chemistry2021
The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodia-driven motility via active β1-integrin in adult tendon cells.
Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Dietary collagen peptides alleviate exercise-induced muscle soreness in healthy middle-aged males: a randomized double-blinded crossover clinical trial.Journal of the International Society of Sports Nutrition · 2023Trial
- Prolyl-Hydroxyproline Promotes Structural Matrix Organization in 3D Equine Tendon Proper and Peritenon Post-Injury Model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Effects of fluoroquinolone antibiotics on extracellular matrix-related phenotypes in tendon cells.Scientific reports · 2026Article
- Microbiota-Driven Metabolic Alterations Induced by BPA, TDCPP and PFOA in an Ex Vivo Human Fecal Fermentation Model.Chemical research in toxicology · 2026Article
- Secretion-based production of prolyl-hydroxylated human type III collagen in scalable Physcomitrella photobioreactors.Plant cell reports · 2026Article
- The role of biotics and bioactive compounds in sports injuries: a narrative review.Frontiers in nutrition · 2026Review
- The Impact of Ageing on Fibrillar Collagens.Sub-cellular biochemistry · 2026Review
- Specific collagen peptides supplementation increases collagen type I content in skeletal muscle after 12 weeks of high-load resistance training: a randomized controlled trial.Frontiers in physiology · 2026Article
- Larval Metabolic and Physiological Mechanisms Underlying Resistance to Chinese Sacbrood Virus inInsects · 2025Article
- Selective effects of collagen-derived peptides Pro-Hyp and Hyp-Gly on the proliferation and differentiation of SSEA3-positive human dental pulp stem cells.Regenerative therapy · 2025Article
- Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Collagen-derived dipeptide prolyl-hydroxyproline cooperates with Foxg1 to activate the PGC-1α promoter and induce brown adipocyte-like phenotype in rosiglitazone-treated C3H10T1/2 cells.Frontiers in nutrition · 2024Article
- Anti-Inflammatory and Antioxidant Properties of a New Mixture of Vitamin C, Collagen Peptides, Resveratrol, and Astaxanthin in Tenocytes: Molecular Basis for Future Applications in Tendinopathies.Mediators of inflammation · 2024Article
- Preventive Effects of Collagen-Derived Dipeptide Prolyl-Hydroxyproline against Dexamethasone-Induced Muscle Atrophy in Mouse C2C12 Skeletal Myotubes.Biomolecules · 2023Article
- Review
- Collagen-Derived Dipeptide Pro-Hyp Enhanced ATDC5 Chondrocyte Differentiation under Hypoxic Conditions.Molecules (Basel, Switzerland) · 2023Article
- Multi-omics analysis reveals substantial linkages between the oral-gut microbiomes and inflamm-aging molecules in elderly pigs.Frontiers in microbiology · 2023Article
- Epithelial-Mesenchymal Transition Induced in Cancer Cells by Adhesion to Type I Collagen.International journal of molecular sciences · 2022Review
- A Comprehensive Review on Collagen Type I Development of Biomaterials for Tissue Engineering: From Biosynthesis to Bioscaffold.Biomedicines · 2022Review
- Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion.NPJ science of food · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Collagen-derived hydroxyproline (Hyp)-containing peptides have a variety of biological effects on cells. These bioactive collagen peptides are locally generated by the degradation of endogenous collagen in response to injury. However, no comprehensive study has yet explored the functional links between Hyp-containing peptides and cellular behavior. Here, we show that the dipeptide prolyl-4-hydroxyproline (Pro-Hyp) exhibits pronounced effects on mouse tendon cells. Pro-Hyp promotes differentiation/maturation of tendon cells with modulation of lineage-specific factors and induces significant chemotactic activity in vitro. In addition, Pro-Hyp has profound effects on cell proliferation, with significantly upregulated extracellular signal-regulated kinase phosphorylation and extracellular matrix production and increased type I collagen network organization. Using proteomics, we have predicted molecular transport, cellular assembly and organization, and cellular movement as potential linked-network pathways that could be altered in response to Pro-Hyp. Mechanistically, cells treated with Pro-Hyp demonstrate increased directional persistence and significantly increased directed motility and migration velocity. They are accompanied by elongated lamellipodial protrusions with increased levels of active β1-integrin-containing focal contacts, as well as reorganization of thicker peripheral F-actin fibrils. Pro-Hyp-mediated chemotactic activity is significantly reduced (p < 0.001) in cells treated with the mitogen-activated protein kinase kinase 1/2 inhibitor PD98059 or the α5β1-integrin antagonist ATN-161. Furthermore, ATN-161 significantly inhibits uptake of Pro-Hyp into adult tenocytes. Thus, our findings document the molecular basis of the functional benefits of the Pro-Hyp dipeptide in cellular behavior. These dynamic properties of collagen-derived Pro-Hyp dipeptide could lead the way to its application in translational medicine.
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Registered trials
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