ArticleThe Journal of biological chemistry2013
Link protein N-terminal peptide binds to bone morphogenetic protein (BMP) type II receptor and drives matrix protein expression in rabbit intervertebral disc cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The trial behind it
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- COMP Is a Biomarker of Cartilage Destruction, Extracellular Matrix and Vascular Remodeling and Tissue Repair.International journal of molecular sciences · 2025Review
- Review
- Link N Directly Targets IL-1β to Suppress Inflammation and Regulate Sensory Pain in Intervertebral Disc Degeneration.Biomolecules · 2025Article
- Short Link N Modulates Inflammasome Activity in Intervertebral Discs Through Interaction with CD14.Biomolecules · 2024Article
- Peptide Regulation of Chondrogenic Stem Cell Differentiation.International journal of molecular sciences · 2023Review
- Single-cell RNA sequencing in orthopedic research.Bone research · 2023Review
- Extracellular matrix in intervertebral disc: basic and translational implications.Cell and tissue research · 2022Review
- A Hyaluronan and Proteoglycan Link Protein 1 Matrikine: Role of Matrix Metalloproteinase 2 in Multiple Myeloma NF-κB Activation and Drug Resistance.Molecular cancer research : MCR · 2022Article
- Chondroinductive/chondroconductive peptides and their-functionalized biomaterials for cartilage tissue engineering.Bioactive materials · 2022Review
- Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs.Bone research · 2021Article
- Simultaneous Recruitment of Stem Cells and Chondrocytes Induced by a Functionalized Self-Assembling Peptide Hydrogel Improves Endogenous Cartilage Regeneration.Frontiers in cell and developmental biology · 2020Article
- The cartilage matrisome in adolescent idiopathic scoliosis.Bone research · 2020Review
- Serum miRNAs are potential biomarkers for the detection of disc degeneration, among which miR-26a-5p suppresses Smad1 to regulate disc homeostasis.Journal of cellular and molecular medicine · 2019Article
- Non-destructive detection of matrix stabilization correlates with enhanced mechanical properties of self-assembled articular cartilage.Journal of tissue engineering and regenerative medicine · 2019Article
- Short Link N promotes disc repair in a rabbit model of disc degeneration.Arthritis research & therapy · 2018Article
- Link protein N-terminal peptide and fullerol promote matrix production and decrease degradation enzymes in rabbit annulus cells.Connective tissue research · 2018Article
- Link N as a therapeutic agent for discogenic pain.JOR spine · 2018Article
- Link Protein N-Terminal Peptide as a Potential Stimulating Factor for Stem Cell-Based Cartilage Regeneration.Stem cells international · 2018Article
- Article
- Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells.Molecular biology of the cell · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Intervertebral disc (IVD) degeneration and associated spinal disorders are leading sources of morbidity, and they can be responsible for chronic low back pain. Treatments for degenerative disc diseases continue to be a challenge. Intensive research is now focusing on promoting regeneration of degenerated discs by stimulating production of the disc matrix. Link protein N-terminal peptide (LPP) is a proteolytic fragment of link protein, an important cross-linker and stabilizer of the major structural components of cartilage, aggrecan and hyaluronan. In this study we investigated LPP action in rabbit primary intervertebral disc cells cultured ex vivo in a three-dimensional alginate matrix. Our data reveal that LPP promotes disc matrix production, which was evidenced by increased expression of the chondrocyte-specific transcription factor SOX9 and the extracellular matrix macromolecules aggrecan and collagen II. Using colocalization and pulldown studies we further document a noggin-insensitive direct peptide-protein association between LPP and BMP-RII. This association mediated Smad signaling that converges on BMP genes leading to expression of BMP-4 and BMP-7. Furthermore, through a cell-autonomous loop BMP-4 and BMP-7 intensified Smad1/5 signaling though a feedforward circuit involving BMP-RI, ultimately promoting expression of SOX9 and downstream aggrecan and collagen II genes. Our data define a complex regulatory signaling cascade initiated by LPP and suggest that LPP may be a useful therapeutic substitute for direct BMP administration to treat IVD degeneration and to ameliorate IVD-associated chronic low back pain.
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Registered trials
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.