Nicotine reduced MMP‐9 expression in the primary porcine tenocytes exposed to cyclic stretch

Abstract

Nicotine is one of the major chemical components of the cigarette smoke, which has been known as a risk factor for tendon ruptures including rotator cuff tears. This study investigated the effect of nicotine on tenocytes under cyclic-stretched condition. Particularly, we focused on the morphologic changes of tenocytes and their expression of MMPs. Primary porcine tenocytes were obtained from the infraspinatus tendon. The cells were cultured on elastic chambers under static or cyclic-stretched condition for 24 h in the existence of nicotine (0, 1, 10, and 100 mM). Cell shape, gene expression of collagen type I and III, MMPs (-1, -2, -3, -9, and -13) and TIMPs (-1, -2, and -3) and enzyme activity of MMP-9 were analyzed using immunohistochemistry, RT-PCR, and zymography. Tenocytes exposed to nicotine represented significantly decreased gene expressions in MMP-9 (p < 0.001) and TIMP-3 (p < 0.05) under the cyclic stretch. Enzymatic activity of MMP-9 was also reduced by nicotine exposure in a dose-dependent manner (p < 0.001). The down-regulation of MMP and TIMP expression by nicotine shown in our in vitro experiment might deteriorate normal metabolism of the tendon. These mechanisms might affect the mechanical properties of the extracellular matrix of the rotator cuff tendon. Keywords: nicotine; tenocyte; matrix metalloproteinase; tendinopathy Cigarette smoke is composed of a large variety of chemical substances which potentially cause addiction and diverse diseases. Several previous authors described that smoking habit constituted a risk factor for rotator cuff tears. Itoi et al.1 showed a positive correlation between the size of rotate cuff tears and the smoking index of the patients: the larger the tear, the greater the smoking index. Kane et al. 2 demonstrated that cadavers of patients with a history of smoking had macroscopic rotator cuff tears and microscopic rotator cuff degeneration more frequently than those without smoking history. Baumgarten et al.3 reported that smoking increased the incidence of rotator cuff tears in a dose-and time-dependent manner from a cohort study. More recently, Carbone et al. 4 analyzed the correlation between smoking habit and size of rotator cuff tear in patients who underwent arthroscopic rotator cuff repair. They concluded that the total number of cigarettes smoked in life had a positive relationship with the size of rotator cuff tear.Among a number of substances contained in the cigarette smoke, nicotine has been recognized as a major component that modulates the pathological processes. 5 We previously employed a rat model to analyze the effect of nicotine on the mechanical properties of tendon. Consecutive exposure to nicotine altered the elastic modulus of the supraspinatus tendon.6 Microstructural changes of the extracellular matrix (ECM) in the tendon tissue seemed to be responsible for the alteration of the mechanical properties by nicotine exposure.Tenocytes synthesize both ECM and matrix metalloproteinases (MMPs). The regulation of MMPs expression plays an ...

The effects of smoking on the expression of gelatinases in chronic periodontitis: a cross-sectional study

“…35,36 Also, cigarette smoke-derived compounds such as nicotine might down-regulate the expression of MMP-9. 37,38 However, in contrast to the present study, Mouzakiti et al 39 demonstrated that smokers presented higher expression of MMP-9 in comparison with non-smokers. Possible explanations for the differences mentioned above among studies may be the severity of periodontitis in the sampling site or the frequency and duration of the smoking habit.…”

Effects of Cigarette Smoking on Elastographic Strain Ratio Measurements of Patellar and Achilles Tendons

“…Although many clinical and laboratory studies concerning the effects of nicotine on healing tendons and ligaments have been reported, 7-9 data regarding the effects of nicotine on healthy tendons are limited in the pertinent literature. 10,[22][23][24][25][26] In addition to studies on the effects of nicotine on tendons, a study by Wright et al 8 examined medial collateral ligament healing after injury of the ligament in a mouse model exposed to 2 cigarettes per day for 2 months. They observed that the healing was worse and the medial collateral ligament was eventually less stiff.…”

Risk Factors for Supraspinatus Tears: A Meta-analysis of Observational Studies

“…A decrease in matrix metalloproteinase expression may directly worsen tendons' metabolism, which in turn affects the mechanical properties of the extracellular matrix of rotator cuff tendons. 19 The above study's 19 results show that some components of cigarettes can produce negative stimulating effects on the generation, apoptosis, and metabolism of muscle cells in vitro. Although these results cannot fully explain why patients who smoke are prone to rotator cuff tears, they can be used to study the relationship between smoking and supraspinatus tears in the future.…”

“…Our study showed that people who smoke are more likely to develop supraspinatus tears (RR, 2.21 [95% CI, 1.56-3.14]). Hatta et al 19 hypothesized that nicotine in cigarettes is a risk factor for rotator cuff tears and studied nicotine’s effect on tendon cells under cyclic stretching. The authors used porcine tendon cells, which are very similar to human tendon cells, and cultured them in the presence of nicotine for 24 hours.…”