Purpose-The purpose of this study was to assess the effect of smoking on supraspinatus tendon degeneration, including cellular alterations, proliferation, and apoptosis of tendon cells.Methods-Supraspinatus tendon samples of 10 smokers and 15 nonsmokers with full-thickness tears were compared, focusing on the severity of tendon histopathology including apoptosis (programmed cell death), cellularity, and proliferation. Immunohistochemistry was used to assess the density of apoptotic cells and proliferation. The extent of tendon degeneration was classified according to a revised version of the Bonar tendon histopathology score.Results-The smokers were younger (P = .01). The symptom duration among smokers was longer (P < .05). The supraspinatus tendons from the smokers presented significantly more advanced degenerative changes (Bonar score, 13.5 [interquartile range, 1.4] v 9 [interquartile range, 3]; P < .001). The smokers' tendons showed increased density of apoptotic cells (0.108 [SE, 0.038] v 0.0107 [SE, 0.007]; P = .024) accompanied by reduced tenocyte density (P = .019) and upregulation of proliferative activity (P < .0001). Conclusions-Smoking is associated with worsened supraspinatus tendon histopathology and increased apoptosis.Clinical Relevance-Pronounced degenerative changes, reduced tendon cellularity, and increased apoptosis may indicate reduced tendon healing capacity in smokers.

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Mast cells and fibroblasts are two key players involved in many fibrotic and degenerative disorders. In the present study we examined the nature of binding interactions between human mast cells and tendon fibroblasts (tenocytes). In the mast cellfibroblast co-culture model, mast cells were shown to spontaneously bind to tenocytes, in a process that was partially mediated by a5b1 integrin receptors. The same receptors on mast cells significantly mediated binding of these cells to tissue culture plates in the presence of tenocyte-conditioned media; the tenocyte-derived fibronectin in the media was shown to also play a major role in these binding activities. Upon binding to tenocytes or tissue culture plates, mast cells acquired an elongated phenotype, which was dependent on a5b1 integrin and tenocyte fibronectin. Additionally, tenocyte-derived fibronectin significantly enhanced mRNA expression of the adhesion molecule, THY1, by mast cells. Our data suggests that a5b1 integrin mediates binding of mast cells to human tenocyte and to tenocyte-derived ECM proteins, in particular fibronectin. Decreased collagen production and increased MMP activities have been detected in tendon biopsies from patients with tendinopathy.3 To date, only a handful of studies have investigated the possible contribution of mast cells in tendinopathy. Mast cells have previously been reported to directly communicate with fibroblasts via gap junction intercellular communications, 4,5 and the SCF/c-kit receptor interaction has been shown to mediate adhesion of mouse mast cells to 3T3 fibroblasts. 6 It is very likely that due to heterogeneity in fibroblast and mast cell populations, different receptors are involved in the process of adhesion, and understanding the exact nature of these specific cell-cell interactions could help delineate these connections.In this study, we utilized an in vitro cell culture system using primary human tendon fibroblasts (tenocytes) and an established human mast cell line (HMC-1) 7 to identify adhesion receptors that mediate binding of human mast cells to tenocytes and their ECM proteins. Mast cells avidly bound to tenocytes upon co-culture, and the adhesion of mast cells to tissue culture plates in response to culture with tenocytederived conditioned media was primarily mediated by a5b1 integrin. Upon binding, mast cells acquired an elongated morphology and enhanced their expression of the adhesion receptor, THY1 (cluster of differentiation 90/CD90), events that were significantly dependent on a5b1 and fibronectin mediated interactions. Our data provides a mechanism by which human mast cells adhere to human tendon fibroblasts and its ECM components. MATERIAL AND METHODS Cell CultureTendon fibroblasts (tenocytes) were isolated from human hamstring tendon. Ethics approval was obtained from the review board at the University of British Columbia.3 Samples of healthy hamstring tendons from living male and female patients undergoing anterior cruciate ligament reconstruction were trimmed to remove fat and muscl...