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

Khan, K.M. and Scott, A., 2009. Mechanotherapy: how physical therapists’ prescription of exercise promotes tissue repair. British journal of sports medicine, 43(4), pp.247-252.

In today’s letter

• Overview of how exercise induces tissue adaptation

• Rapid Results = Exercise promotes soft tissue adaptation in a 3-step process

1. Mechano-coupling

2. Cell–cell communication

3. The effector response

• 3 Reads to check out to further you knowledge about …

• Meme of the week: What did we do again? 🫠 

Aim of the study

This paper outlines current scientific knowledge on using load to therapeutically stimulate tissue repair and remodelling in tendons, muscles, cartilage, and bone.

Did you know?

Mechanotransduction is the process by which the body converts mechanical loading into cellular responses.

These cellular responses lead to structural changes. An example is bone adapting to load, where a small, weak bone becomes larger and stronger due to appropriate load through mechano-transduction.

Mechano-transduction involves three steps:

1. Mechanocoupling

2. Cell–cell communication

3. The effector response

To explain to patients, these steps can be simplified as:

1. The mechanical trigger or catalyst

2. Communication throughout a tissue to distribute the loading message

3. The cellular response that produces and assembles necessary materials in correct positions

Communication at each stage happens through cell signaling, an information network involving messenger proteins, ion channels, and lipids.

 Step 1 - Mechano-coupling

Or in other words, the trigger (Exercise)

• Mechanocoupling occurs when physical loads, such as shear or compression, cause a disturbance to the cells within a tissue.

• For instance, each walking step puts tensile stress on the Achilles tendon from the calf complex, subjecting its cells to tensile and shearing forces.

• Tendons also undergo compression forces, which can deform the cells and trigger various responses based on the load's type, magnitude, and duration.

 Step 2 - Cell to Cell communication

Or in other words - Communication throughout a tissue to distribute the loading message

• The previous paragraph illustrated mechanocoupling by focusing on a single cell, but let us draw back to examine a larger tissue area that contains thousands of cells embedded within an extracellular matrix (image below).

• The signalling proteins for this step include calcium and inositol triphosphate. The process of cell to cell communication is best understood by illustration

• The critical point is that stimulus in one location (location ‘‘1’’ in the image C) leads to a distant cell registering a new signal (location ‘‘2’’ in the image E) even though the distant cell does not receive a mechanical stimulus.

Step 3 - Effector cell response

Or in other words - The cellular response that produces and assembles necessary materials in correct positions

• To illustrate the 3rd part of mechano-transduction (effector cell response), lets focus on the boundary between the extracellular matrix and a single cell.

• This process can be used in mechano-therapy to promote tissue repair and remodelling.

• While the main steps of mechano-transduction for bone connective tissues are well understood, there are still unknown elements in the load-induced signalling pathways for muscle, tendon, and articular cartilage.

• Mechanotransduction is a continuous physiological process in the human body, similar to respiration and circulation.

• The skeleton serves as an example of connective tissue, with the osteocyte network acting as the body’s sensor, a process known as the "mechanostat."

• Inactivity leads to a weak mechano-transduction signal, resulting in connective tissue loss (e.g., osteoporosis).

• When loads exceed the tissue’s set point, mechano-transduction stimulates the body to adapt by increasing protein synthesis and adding tissue, resulting in larger, stronger bones

Tendon

• Tendon is a dynamic,load responsive tissue. One significant load-induced response in tendons is the up-regulation of insulin-like growth factor (IGF-I).

• IGF-I up-regulation is linked to cellular proliferation and matrix remodelling within the tendon.

• Studies suggest other growth factors and cytokines, in addition to IGF-I, also play a role.

• Alfredson et al. used grey-scale ultrasound to examine 26 tendinopathic Achilles tendons treated with eccentric exercise, finding that 19 of them showed a more normalised structure after 3.8 years.

• This and other studies demonstrate that tendons can respond favourably to controlled loading after injury.

Muscle

• Muscle is highly responsive to load, making it ideal for studying load-induced pathways.

• Overload causes immediate, local up-regulation of mechanogrowth factor (MGF), a splice variant of IGF-I with unique effects.

• MGF expression leads to muscle hypertrophy by activating satellite cells.

• Loading benefits include better alignment of regenerating myotubes, faster and more complete regeneration, and reduced atrophy of surrounding myotubes.

Articular cartilage

• Like other musculoskeletal tissues, articular cartilage contains mechano-sensitive cells (chondrocytes) that signal through similar pathways.

• Alfredson and Lorentzon treated 57 patients with full-thickness patellar cartilage defects and long-term knee pain using periosteal transplantation, with or without continuous passive motion (CPM).

• 76% of patients using CPM had an "excellent" outcome, compared to 53% without CPM.

• Although tissue repair was not directly assessed, the results suggest the need for further research into tissue response and optimisation of loading parameters.

Bone

• In bone, osteocytes are the primary mechano-sensors.

• A clinical study suggested that mechano-transduction can be utilised by physiotherapists to improve fracture healing.

• In the study, 21 patients with distal radius fractures were randomised to receive either standard care with immobilisation and gripping exercises, or standard care plus intermittent compression via an inflatable pneumatic cuff worn under the cast.

• The experimental group showed significantly increased strength (12–26%) and range of motion (8–14%) at the end of the immobilisation period.

• These improvements were maintained at 10 weeks.

Top 3 resources

To further your knowledge about tissue adaptation to exercises

1. Building strength in early stage rehab - LINK

2. Nutrition & training to prevent soft tissue injury - LINK

3. Tissue adaptation to exercise, the full shabang (Lecture) - LINK

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