Cellular Mechanisms Involved in Muscle Pathology

Summary

The overall purpose of this proposed study is the understanding of cellular mechanisms involved in the pathologic fatty degeneration of muscle. Fatty infiltration in skeletal muscle is observed following sports injuries such as muscle strain injuries and Achilles tendon rupture. It is also observed in the degenerative state after rotator cuff tears as well as in the aging process. While fatty degeneration of skeletal muscle occurs in many different conditions and is known to decrease muscle function, the cellular processes involved in fatty infiltration have not been investigated in human muscle. Hypotheses: 1. There is a high amount of fibro-adipogenic progenitors (FAPs) with an adipogenic pattern in pathologic skeletal muscle following a muscle strain injury and a full Achilles tendon rupture. We hypothesize that there is an increased number of FAPs with an adipogenic signature already in the acute phase after a strain injury, but a significantly higher number in the chronic stage as well as in the muscle following an Achilles tendon rupture. 2. Mechanical cues are a major driver of the phenotypic drift of FAPs. The lack of mechanical stimuli initiates the adoption of an adipogenic pathway in naïve FAPs, whereas naïve FAPs exposed to mechanical stimuli will maintain their undifferentiated phenotype. 3. The adherence of FAPs to a soft material will activate the adoption of an adipogenic phenotype, whereas a stiff material will favor a more fibrotic phenotype in naïve FAP's isolated from healthy skeletal muscle.

Eligibility

Inclusion Criteria:

* 18 years and older, male and female, with an acute muscle strain injury (\<14 days post injury) in the calf or hamstring muscles (group 1). Pathological changes visible on an ultrasound scan as hypoechoic areas.
* 18 years and older, male and female, with a chronic muscle strain injury (\> 6 months prior to inclusion) in the calf or hamstring muscles (group 2), sequela including recurrent strain injuries, pain and/ or decrease in muscle function. Pathological changes visible on an ultrasound scan as hypo-/ hyperechoic areas.
* 18 years and older, male and female, with a full Achilles tendon rupture (\> 1 year prior to inclusion) with pathological changes: Fatty degeneration visible on an ultrasound scan (group 3).

Exclusion Criteria:

* Type I and II Diabetes, Connective tissue and/or rheumatic diseases, or any observed organ dysfunctions
* Daily smoking
* Persons with daily intake of non-steroidal anti-inflammatory drugs (NSAIDs) within three months prior to time of contact
* Allergic reactions to local anesthesia
* Use of anticoagulant treatment
* Needle phobia
* Any drug or alcohol abuse now or in the past
* The absence of any pathological changes visible on an ultrasound scan as hypo-/ hyperechoic areas (group 1 and 2)
* The absence of any pathological changes (fatty degeneration) in either the gastrocnemius or the soleus muscle visible on an ultrasound scan (Subject group 3)

Conditions5

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