Tendon Remodeling in Response to Resistance Training, Anabolic Androgenic Steroids and Aging

Abstract

Exercise training (ET), anabolic androgenic steroids (AAS), and aging are potential factors that affect tendon homeostasis, particularly extracellular matrix (ECM) remodeling. The goal of this review is to aggregate findings regarding the effects of resistance training (RT), AAS, and aging on tendon homeostasis. Data were gathered from our studies regarding the impact of RT, AAS, and aging on the calcaneal tendon (CT) of rats. We demonstrated a series of detrimental effects of AAS and aging on functional and biomechanical parameters, including the volume density of blood vessel cells, adipose tissue cells, tendon calcification, collagen content, the regulation of the major proteins related to the metabolic/development processes of tendons, and ECM remodeling. Conversely, RT seems to mitigate age-related tendon dysfunction. Our results suggest that AAS combined with high-intensity RT exert harmful effects on ECM remodeling, and also instigate molecular and biomechanical adaptations in the CT. Moreover, we provide further information regarding the harmful effects of AAS on tendons at a transcriptional level, and demonstrate the beneficial effects of RT against the age-induced tendon adaptations of rats. Our studies might contribute in terms of clinical approaches in favor of the benefits of ET against tendinopathy conditions, and provide a warning on the harmful effects of the misuse of AAS on tendon development.

Keywords: aging; anabolic androgenic steroids; extracellular matrix; resistance training; tendon.

Figure 1

Structure of tendon. The tendon is composed of type I collagen fibers. Type I collagen is the major structural component of the tendon. Col1a1 and Col1a2 code for collagen α1(I) and α2(I) polypeptides, respectively. Type I collagen triple-helical molecules containing two α1(I) and one α2(I) chains assemble into fibrils that combine to form fibers. Tendon fibroblasts reside between collagen fibers. Fibers are surrounded by a connective tissue, the endotendon, which also contains fibroblasts. Fibers combine to form fascicules. Tendons are ensheathed by an outer layer of connective tissue (epitendon), which is surrounded by another layer of connective tissue (paratendon). Together, the epitendon and paratendon external sheaths constitute the peritendon. Adapted from Nourissat et al. 2015 [30] and Lipman et al. 2018 [56].

Figure 2

Integrative model based on our findings, indicating the major effects of AAS, RT, and aging on tendons of rats. AAS—anabolic androgenic steroids; RT—resistance training; COL-I—type I collagen; COL-III—type III collagen; COL1A1—type I collagen-α1; COL3A1—type III collagen-α1; TIMP-1—tissue inhibitor of metalloproteinase 1; TIMP-2—tissue inhibitor of metalloproteinase 2; MMP-2—metalloproteinase 2; IGF-IEa—insulin-like growth factor I-Ea; CTGF—connective tissue growth factor; TGFβ-1—transforming growth factor beta 1; VEGF—vascular endothelial growth factor; Bgn—biglycan; Fmod—fibromodulin; COMP—cartilage oligomeric matrix protein; FABPH—acid-binding protein heart; FABP4—acid-binding protein-4; GELS—gelsolin; S100A6—protein S-100A6; TRFE—serotransferrin; ALBU—serum albumin; CAH3—carbonic anhydrase; PRVA—parvalbumin alpha.