ArticlePloS one2011
Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The peripheral neuronal phenotype is important in the pathogenesis of painful human tendinopathy: a systematic review.Clinical orthopaedics and related research · 2013Pooled it
- PET-scan shows peripherally increased neurokinin 1 receptor availability in chronic tennis elbow: visualizing neurogenic inflammation?PloS one · 2013Trial
- Both Radiofrequency Microtenotomy and Physical Therapy Provide Significant Improvements in Patients With Chronic Midportion Achilles Tendinopathy at a Minimum 5-Year Follow-Up.Arthroscopy, sports medicine, and rehabilitation · 2026Article
- Computed microtomographic imaging of revascularization during healing of Achilles tendon injury.Journal of anatomy · 2025Article
- Tendon mechanobiology in the context of tendon biofabrication.Frontiers in bioengineering and biotechnology · 2025Review
- MRGPRX2-mediated mast cell activation by substance P from overloaded human tenocytes induces inflammatory and degenerative responses in tendons.Scientific reports · 2024Article
- Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts.International journal of molecular sciences · 2024Article
- The roles and therapeutic potentialof mesenchymal stem/stromal cells and their extracellular vesicles in tendinopathies.Frontiers in bioengineering and biotechnology · 2023Review
- Exosomes derived from human umbilical cord mesenchymal stem cells reduce tendon injuries via the miR-27b-3p/ARHGAP5/RhoA signaling pathway.Acta biochimica et biophysica Sinica · 2022Article
- The Effect of Age and Intrinsic Aerobic Exercise Capacity on the Expression of Inflammation and Remodeling Markers in Rat Achilles Tendons.International journal of molecular sciences · 2021Article
- Maintenance of Ligament Homeostasis of Spheroid-Colonized Embroidered and Functionalized Scaffolds after 3D Stretch.International journal of molecular sciences · 2021Article
- Cyclically stretched ACL fibroblasts emigrating from spheroids adapt their cytoskeleton and ligament-related expression profile.Cell and tissue research · 2021Article
- The expression of substance P and calcitonin gene-related peptide is associated with the severity of tendon degeneration in lateral epicondylitis.BMC musculoskeletal disorders · 2021Article
- A Functional High-Load Exercise Intervention for the Patellar Tendon Reduces Tendon Pain Prevalence During a Competitive Season in Adolescent Handball Players.Frontiers in physiology · 2021Article
- Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury.Connective tissue research · 2020Article
- Sensory Neuropeptides and their Receptors Participate in Mechano-Regulation of Murine Macrophages.International journal of molecular sciences · 2019Article
- Crosstalk between neuropeptides SP and CGRP in regulation of BMP2-induced bone differentiation.Connective tissue research · 2018Article
- The roles of inflammatory mediators and immunocytes in tendinopathy.Journal of orthopaedic translation · 2018Review
- Substance P modulates bone remodeling properties of murine osteoblasts and osteoclasts.Scientific reports · 2018Article
- A Protocol to Acquire the Degenerative Tenocyte from Humans.Journal of visualized experiments : JoVE · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
It has been hypothesised that substance P (SP) may be produced by primary fibroblastic tendon cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hypercellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A cell culture model of primary human tendon cells was used. The vast majority of tendon cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these cells. Gene expression analyses showed that mechanical loading (strain) of tendon cell cultures using the FlexCell© technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded tendon cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10⁻⁷ M. SP exposure furthermore resulted in increased cell metabolism, increased cell viability, and increased cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.
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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.