Molecular Signatures of Muscle Rehabilitation After Limb Disuse

We have identified the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. Subjects with a closed malleolus fracture treated conservatively with 6 weeks of cast immobilization are recruited. Then subjects are enrolled in a 6 weeks structured rehabilitation program focusing on progressive resistance training of the ankle plantar flexor muscles. Phenotypic measurements are performed before (pre-rehab), during (mid-rehab, 3 weeks) and immediately after (post-rehab, 6 weeks) the rehabilitation intervention. The maximal cross-sectional area (muscle size) and peak torque (muscle strength) are quantified using isometric and isokinetic tests in combination with 3D-magnetic resonance imaging. Ankle plantar flexor muscle size and strength measurements are also performed on the uninvolved limb (serves as a control) at 4 months post-immobilization. Measurements are also acquired from the contralateral leg, which serves as an internal control. Four longitudinal muscle biopsies are taken from the medial gastrocnemius of each subject and expression profiled over the entire human genome (U133 plus2). Muscle biopsies are taken at the following time points: before (pre-rehab; post-immobilization), after 3 weeks of rehabilitation (early transcriptional changes) and immediately after 6 weeks of rehabilitation (chronic transcriptional changes). An additional muscle biopsy is taken at 4 months post-immobilization from the uninvolved (contralateral) medial gastrocnemius, which serves as a control sample. The subjects are grouped based on their % change of MRI with 6% as the cutoff value. Immobolization: high responders- AFX006, AF007, AFX015, AFX017, AFX020, AFX022, AFX023, AFX024 low responders- AFX012, AFX013, AFX019, AFX021 Rehabilitation: high responders- AFX006, AFX007, AFX015, AFX016, AFX017, AFX020, AFX022, AFX023, AFX024 low responders- AFX009, AFX010, AFX011, AFX012, AFX013, AFX019, AFX021