Green Tea and Glycine Modulate the Activity of Metalloproteinases and Collagen in the Tendinitis of the Myotendinous Junction of the Achilles Tendon

Abstract

The myotendinous junction (MTJ) is the weakest element in the muscle-tendon unit of the heel, and thus the most susceptible to injuries. The scarcity of adequate treatments means that tendinitis is a major concern to athletes and other groups who depend on their physical fitness, although green tea and glycine have both been shown to have beneficial effects on the inflammation. The present study investigated the remodeling effects of green tea and glycine in the MTJ of rats with tendinitis. For this, male Wistar rats were divided into five groups: animals without tendinitis and animals with tendinitis; animals with tendinitis supplied with green tea; animals with tendinitis supplied with a glycine diet; animals with tendinitis supplied with a green tea and glycine diet. Tendinitis was induced and the treatment with green tea (700 mg/kg/day) and a 5% glycine diet lasted 7 days. The treatments regulated the activity of metalloproteinases (MMP)-2, -8, and -9, and induced the synthesis of type I collagen, glycosaminoglycans, and noncollagenous proteins. Changes were also noted in the compaction of the collagen molecules and the amount of tenocytes. When combined, green tea and glycine modulated the inflammatory process and induced the synthesis of the elements involved in the post-lesion recovery of the tissue. The data from the MTJ were different when compared with results already published using the whole Achilles tendon. These data indicate that each region of the inflamed tendon can exhibit different responses

A Natural Hydrogel with Prohealing Properties Enhances Tendon Regeneration

“…Glycine is beneficial for tendon healing. For example, when a 5% glycine diet was provided to rats with an Achilles tendon injury, increased collagen deposition was observed after 7 d. [ 28 ]…”

“…The large pore size could also benefit the transport of nutrients and oxygen and promote regeneration. [ 26 ] The SSAD‐derived hydrogel could provide glycine [ 27–29 ] for collagen synthesis and release insulin‐like growth factor (IGF)‐1 and stromal cell‐derived factor (SDF)‐1 to recruit stem cells, promote cell proliferation, and produce additional collagen. [ 30–32 ] Furthermore, we hypothesized that the SSAD‐derived hydrogel with a relatively small pore size of 3–4 µm could reduce peritendinous adhesion, as at this density, it could block the invasion of fibroblastic cells from the surrounding tissues, serving as a physical barrier.…”

Modulation of Inflammation by Plant-Derived Nutraceuticals in Tendinitis

“…With regard to chronic musculoskeletal disorders, such as RA, osteoporosis, or OA, various polyphenols have been found to reduce inflammation and, in addition, exhibit tissue-protective and regeneration-stimulating effects [ 36 , 92 , 93 , 125 ] due to their ability to modulate dysregulated pro-inflammatory pathways back to physiological conditions, and, more so, to stimulate anabolic processes in the respective tissues, helping them to regenerate and heal [ 36 , 126 , 127 , 128 , 129 ]. Additionally, in tendinitis, as a very common and painful condition disabling musculoskeletal functionality and still lacking sustainable treatment, various plant-derived compounds have been demonstrated to affect inflammation and promote tissue healing, thus representing promising bio-active treatment agents in tendinitis therapy [ 10 , 14 , 36 , 62 , 65 , 130 , 131 , 132 , 133 ]. Since plant-derived nutraceuticals are ingredients of a large number of vegetables, spices, and fruit, they can be easily integrated into people’s daily diet while being cost-effective [ 134 , 135 , 136 ].…”

“…As of recent, various polyphenols have been proven to show inflammation-protective activity in disordered tendon tissue, including compounds of turmeric, calebin A and curcumin, green tea extracts, various flavones, pineapple extract bromelain, boswellia acid, and resveratrol, among several others [ 10 , 14 , 36 , 130 , 143 , 144 , 145 ]. The main target pathways that have been found to be modulated by nutraceuticals specifically in tendinitis are NF-κB, STAT3, PI3K, and associated pathway dependent gene products (such as MMPs, COX-2, and caspase-3), as well as stimulated cytokines, including IL-1β, TNF-α, and TNF-β ( Figure 3 ) [ 10 , 36 , 132 , 146 , 147 ]. With nutraceuticals targeting NF-κB, translocation from cell cytoplasm into the nucleus is suppressed, inhibiting its activation.…”

“…In addition, the synthesis of collagen I as a crucial constituent of tendon was remarkably enhanced by green tea treatment. Simultaneously, inflammatory pathways were modulated in the form of decreased MMP-9 levels, which is important for the remodeling of tissue, whereas MMP-2 and IL-1β, both involved in the active remodeling process, remained elevated during green tea treatment, indicating the potential of green tea polyphenols to accelerate tendon tissue remodeling and the regeneration after tendinitis [ 132 , 177 ]. Altogether, several studies indicate that green tea extracts and EGCG represent promising agents when it comes to fighting ROS and inflammation-triggering stimuli, as well as inflammation itself in tendon tissue ( Table 1 ).…”