Mast cells exert pro-inflammatory effects of relevance to the pathophyisology of tendinopathy
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RESEARCH ARTICLE
Open Access
Mast cells exert pro-inflammatory effects of relevance to the pathophyisology of tendinopathy Hayedeh Behzad, Aishwariya Sharma, Rouhollah Mousavizadeh, Alex Lu and Alex Scott*
Abstract Introduction: We have previously found an increased mast cell density in tendon biopsies from patients with patellar tendinopathy compared to controls. This study examined the influence of mast cells on basic tenocyte functions, including production of the inflammatory mediator prostaglandin E2 (PGE2), extracellular matrix remodeling and matrix metalloproteinase (MMP) gene transcription, and collagen synthesis. Methods: Primary human tenocytes were stimulated with an established human mast cell line (HMC-1). Extracellular matrix remodeling was studied by culturing tenocytes in a three-dimensional collagen lattice. Survival/proliferation was assessed with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. Levels of mRNA for COX-2, COL1A1, MMP1, and MMP7 were determined by quantitative real-time polymerase chain reaction (qPCR). Cox-2 protein level was assessed by Western blot analysis and type I procollagen was detected by immunofluorescent staining. PGE2 levels were determined using an enzyme-linked immunosorbent assay (ELISA). Results: Mast cells stimulated tenocytes to produce increased levels of COX-2 and the pro-inflammatory mediator PGE2, which in turn decreased COL1A1 mRNA expression. Additionally, mast cells reduced the type I procollagen protein levels produced by tenocytes. Transforming growth factor beta 1 (TGF-β1) was responsible for the induction of Cox-2 and PGE2 by tenocytes. Mast cells increased MMP1 and MMP7 transcription and increased the contraction of a three-dimensional collagen lattice by tenocytes, a phenomenon which was blocked by a pan-MMP inhibitor (Batimastat). Conclusion: Our data demonstrate that mast cell-derived PGE2 reduces collagen synthesis and enhances expression and activities of MMPs in human tenocytes.
Introduction Tendons are dense connective tissues, responsible for transmitting load between muscle and bone. The primary cell type in tendons, tenocytes, may be influenced by the presence of mast cells in their microenvironment. Although associations between mast cells and a number of chronic conditions including pulmonary fibrosis [1], renal fibrosis [2], and scleroderma [3] have been established, very few data are available on the possible link between mast cells and the failed tissue healing or fibrosis that is evident in chronically injured tendon tissues. We have previously documented a greater number of mast cells in * Correspondence: [email protected] Department of Physical Therapy, UBC, 2635 Laurel Street, Vancouver, BC V5Z 1M9, Canada
the tendons of patellar tendinopathy subjects compared with healthy controls [4], and increased mast cell numbers have also been detected in the injured rotator cuff [5]. We also found that tendon overuse (intensive uphill treadmill running) led to an increa
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