Figure 1. Tissue homeostasis in the neuromuscular–tendon–connective tissue complex.

A simplified overview of the different factors involved in the short‐ and long‐term regulation of the triceps surae muscle, tendon and connective tissue. When we use the muscles, neural activity not only signals contraction of the muscle, but also initiates a cascade of signalling factors, which determines the growth of the muscle fibres, the phenotype of the muscle fibres and the properties of the connective tissue, as well as increasing the capillary network in the muscle. As a result of the mechanical stimuli during muscle activity, for instance from the impact of heel strike when we walk, a myriad of different cells are activated, including mechanosensitive fibroblasts, which results in connective and muscle tissue changes. Concomitantly, vascular and metabolic factors are activated in order to meet the energy and metabolic needs of the muscle and connective tissue, when activated. Finally, muscle, tendon and connective tissue elicit signals to the nervous system regarding the present state of the tissue, which is incorporated into the immediate and future neural signalling. The different tissues are thus part of an integrated network that regulates the environment of the cells and maintains a number of key factors (the contractile properties of the muscle, the stiffness of the tissue) within relatively strict limits. Additionally, genetic and epigenetic factors affect the composition of the tissues, thus influencing the capability of the tissue to react and adapt to changes in the tissue homeostasis. This homeostasis is what we observe as a normal and healthy tissue. Alteration in one of the factors involved in the network will inevitably result in adaptive changes throughout the network, in order to maintain homeostasis as far as possible. However, if the alteration is too big the network cannot maintain normal homeostasis and will settle on a new (unhealthy, pathological) set value of homeostasis. This is the state where pathological contractures have developed. In this review we will discuss the possible key contributors to the development of contractures in this homeostatic network. AMPK, 5‐AMP‐activated protein kinase; FAK, focal adhesion kinase; mn, motor neuron; NFAT, nuclear factor of activated T‐cells.