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S

oft tissues (muscle, tendon and ligaments) demonstrate

a graded capacity to respond to the impact of external

stimuli with molecular and cellular adjustments that

improve their capacity to withstand the original impact. The

diagnostic assessment of the adaptive potential of muscles

provides indications on how bottlenecks in the current

therapy of musculoskeletal defects can be overcome. The aim

being to innovate surgical and rehabilitative approaches to

permit the handicapped individual to maximise adaptive

stimuli and processes.

Muscle health is an economic factor

Plasticity is described as the ability of an organism to change its

phenotype in response to changes in the environment. This has its

place in body homeostasis, especially regarding the implication of

skeletal muscle in bodily actions. Through its mechanical actions

in locomotion, posture and speech, muscle facilitates interactions

with the environment and affects energy expenditure. The

reduction of muscles’ functional ability thus develops an

important negative impact on our human capacity.

Muscle weakness and associated poor fatigue resistance is a

major challenge to modern Western society. It arises due to a

reduction in the force-producing capacity of skeletal muscle with

prolonged inactivity (disuse), injury or disease. The consequent

reduction in strength negatively affects physical fitness and

mobility, which lowers the quality of life. Based on epidemiological

evidence it is estimated that associated costs accrue to CHF

2,000 (~€1,906) per person per year (Fig. 1). Musculoskeletal

health is thus an important financial substrate in Western society.

Our research focus

The strategic aim of the Laboratory for Muscle Plasticity at Balgrist

University Hospital is to expose the molecular and cellular

mechanisms underpinning muscle affections in clinical situations

ranging from simple exertion-induced soreness to major

musculoskeletal disease of striated muscle, and more so their

reversion with rehabilitation. This is done within the goal to identify

biological bottlenecks, which opens venues for novel interventions

that can halt muscle deconditioning and degeneration. Specific

emphasis is put on the myocellular processes of rehabilitative and

therapeutic measures after orthopaedic surgery. Towards this end

we focus on patient groups which could benefit from an

improvement in muscle function. Further, we assess transfer

effects on musculoskeletal health and quality of life.

Research approach and strategy

The Laboratory for Muscle Plasticity at Balgrist deploys state-of-

the-art methodology to optimise surgical approaches and

rehabilitation based on genetic and physical constitution. The

research is embedded in the Orthopaedic Hospital of the University

of Zurich. By 2016 it will extend its patient-tailored biomedical

research by integrating its activities in the musculoskeletal research

centre at Balgrist campus. The following sections highlight active

areas and the scientific background of our research towards a

personalised approach to musculoskeletal health.

Background

Skeletal muscle function relies on shortening of the embedded

muscle cells (fibres) and this depends on bioenergetic processes.

This results in the capacity for force production, which is dictated

by the composition and anatomy of skeletal muscle. This especially

implicates the volume content of slow and fast contractile types of

myofibrils, mitochondria and capillaries. These cellular variables

define the maximal force (strength) and fatigue resistance of

contraction. Both features are conditioned in a pulsatile manner by

muscle use. This occurs because there is a natural degradation of

muscle material due to wear and tear of cellular structures. The

wasted muscle material must be replaced through the activation of

biosynthesis. Mechanical stress with weight-bearing contractions is

a potent stimulus for the activation of these synthetic pathways.

Energy flux is its most important modulator. The specific

conditioning of muscle through physiological factors is amply

illustrated by the different outcome of strength-type

versus

endurance-type sports activities that involve a high load or high

repetition number of contractions, respectively.

The underlying regulation involves the activation of a molecular

programme that is embedded in our genes and which dictates the

proteins to be made, i.e. expressed. The study of gene expression

allows exposing the mechanistic relationship between the dose

and duration of exercise and the resulting effect on muscle

function. This knowledge is important to develop rehabilitative

The Laboratory for Muscle Plasticity is constantly exploring and researching in its

quest to perfect muscle function

A quest into muscle plasticity

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I S S U E S E V E N

H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L

www.horizon2020projects.com

P R O F I L E

S O C I E TA L C H A L L E N G E S : H E A L T H & W E L L B E I N G

Fig. 1 Healthcare cost in 2011 of the seven major

non-transmissive diseases. To the right: focus on affliction of the

musculoskeletal system