Alterations in Skeletal Muscle Gene Expression Following Total Knee Arthroplasty
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Knee Osteoarthritis
- Sponsor
- University of Colorado, Denver
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Catabolic gene expression
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The overall goals of this work are: 1) to elucidate alterations in gene expression and downstream protein synthesis 2 weeks after Total Knee Arthroplasty (TKA) to better explain quadriceps muscle atrophy after TKA and 2) understand the mechanisms responsible for improved maintenance of muscle strength with Neuromuscular Electrical Stimulation (NMES) utilization. Furthermore, this investigation seeks to expand previous findings regarding attenuation of strength and functional performance deficits with NMES application to better understand how altered gene expression influences muscle function.
Investigators
Eligibility Criteria
Inclusion Criteria
- •50 to 75 years of age
- •Scheduled for unilateral TKA at University of Colorado Hospital
- •Diagnosed with osteoarthritis
- •Cognitive status that allows patients to consistently comprehend and repeat back directions regarding the details of the study
Exclusion Criteria
- •Neurological, vascular or cardiac problems that significantly limit function
- •BMI \> 35
- •Testosterone supplementation
- •Pregnancy
- •Anticoagulant therapy
Outcomes
Primary Outcomes
Catabolic gene expression
Time Frame: Change in gene expression from immediately pre surgery to 2 weeks after surgery
Standard procedures including total RNA isolation, cDNA synthesis, cRNA labeling, microarray hybridization and image acquisition will be performed. Protein content (translation of MAFbx, MuRF1, myostatin) will be analyzed. Total RNA (500 ng) will be reverse transcribed with the iScript cDNA synthesis kit (Bio-Rad, Hercules, CA), and quantitative PCR will be performed using primer sets for genes of interest, reference genes and iQ SYBR Supermix (Bio-Rad) following manufacturer's protocols.
Secondary Outcomes
- Changes in quadriceps strength(3 days Pre operative and 2 weeks post operative)
- Changes in quadriceps size(3 days Pre operative and 2 weeks post operative)
- Muscle Fiber Cross-Sectional Area(Immediately pre surgery to 2 weeks after surgery)
- Changes in neural cell adhesion molecule (NCAM) concentration(Preop and 2 weeks postop)
- Functional Performance Measures (4 meter walk test, timed up and go, stair climbing test)(3 days Pre operative and 2 weeks post operative)
- Anabolic Gene Expression(Immediately pre surgery to 2 weeks after surgery)
- Changes in quadriceps activation(3 days Pre operative and 2 weeks post operative)