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- Backman, LudvigUmeå universitet,Anatomi,Idrottsmedicin (author)
Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation
- Article/chapterEnglish2011
Publisher, publication year, extent ...
- 2011-11-01
- San Francisco, USA :Public Library of Science,2011
- electronicrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:umu-50694
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-50694URI
- https://doi.org/10.1371/journal.pone.0027209DOI
Supplementary language notes
- Language:English
- Summary in:English
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- SwePubSwePub
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Notes
- 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 (R) 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.
Subject headings and genre
- NATURVETENSKAP Biologi hsv//swe
- NATURAL SCIENCES Biological Sciences hsv//eng
Added entries (persons, corporate bodies, meetings, titles ...)
- Fong, GloriaUmeå universitet,Anatomi(Swepub:umu)glfo0001 (author)
- Andersson, GustavUmeå universitet,Anatomi(Swepub:umu)guvann04 (author)
- Scott, AlexanderVancouver Coastal Health and Research Institute, University of British Columbia, Vancouver (author)
- Danielson, PatrikUmeå universitet,Anatomi(Swepub:umu)pakdan00 (author)
- Umeå universitetAnatomi (creator_code:org_t)
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- In:PLOS ONESan Francisco, USA : Public Library of Science6:11, s. e27209-1932-6203
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