Mechanotherapy: how physical therapists' prescription of exercise promotes tissue repair

Abstract

Mechanotransduction is the physiological process where cells sense and respond to mechanical loads. This paper reclaims the term "mechanotherapy" and presents the current scientific knowledge underpinning how load may be used therapeutically to stimulate tissue repair and remodelling in tendon, muscle, cartilage and bone. The purpose of this short article is to answer a frequently asked question "How precisely does exercise promote tissue healing?" This is a fundamental question for clinicians who prescribe exercise for tendinopathies, muscle tears, non-inflammatory arthropathies and even controlled loading after fractures. High-quality randomised controlled trials and systematic reviews show that various forms of exercise or movement prescription benefit patients with a wide range of musculoskeletal problems.1(-)4 But what happens at the tissue level to promote repair and remodelling of tendon, muscle, articular cartilage and bone? The one-word answer is "mechanotransduction", but rather than finishing there and limiting this paper to 95 words, we provide a short illustrated introduction to this remarkable, ubiquitous, non-neural, physiological process. We also re-introduce the term "mechanotherapy" to distinguish therapeutics (exercise prescription specifically to treat injuries) from the homeostatic role of mechanotransduction. Strictly speaking, mechanotransduction maintains normal musculoskeletal structures in the absence of injury. After first outlining the process of mechanotransduction, we provide well-known clinical therapeutic examples of mechanotherapy-turning movement into tissue healing.

Conflict of interest statement

Competing interests: None.

Figures

Figure 1

Tendon cell undergoing (A,B) shear and (C) compression during a tendon-loading cycle.

Figure 2

Tendon tissue provides an example of cell–cell communication. (A) The intact tendon consists of extracellular matrix (including collagen) and specialised tendon cells (arrowheads). (B) Tendon with collagen removed to reveal the interconnecting cell network. Cells are physically in contact throughout the tendon, facilitating cell–cell communication. Gap junctions are the specialised regions where cells connect and communicate small charged particles. They can be identified by their specific protein connexin 43. (C–E) Time course of cell–cell communication from (C) beginning, through (D) the midpoint to (E) the end. The signalling proteins for this step include calcium (red spheres) and inositol triphosphate (IP3).

Figure 3

Mechanical loading stimulates protein synthesis at the cellular level. (A) A larger scale image of the tendon cell network for orientation. We focus on one very small region. (B) Zooming in on this region reveals the cell membrane, the integrin proteins that bridge the intracellular and extra-cellular regions, and the cytoskeleton, which functions to maintain cell integrity and distribute mechanical load. The cell nucleus and the DNA are also illustrated. (C) With movement (shearing is illustrated), the integrin proteins activate at least two distinct pathways. (D) One involves the cytoskeleton that is in direct physical communication with the nucleus (ie, tugging the cytoskeleton sends a physical signal to the cell nucleus). Another pathway is triggered by integrins activating a series of biochemical signalling agents which are illustrated schematically. After a series of intermediate steps those biochemical signals also influence gene expression in the nucleus. (E). Once the cell nucleus receives the appropriate signals, normal cellular processes are engaged. mRNA is transcribed and shuttled to the endoplasmic reticulum in the cell cytoplasm, where it is translated into protein. The protein is secreted and incorporated into extracellular matrix. (F) In sum, the mechanical stimulus on the outside of the cell promotes intracellular processes leading to matrix remodelling.