Muscle Inflammation Susceptibility: A Potential Prognostic Factor For Optimal Post-Surgical Rehabilitation

Many individuals with end-stage osteoarthritis undergo elective total hip/knee arthroplasty (THA/TKA) to relieve pain and improve mobility and quality of life. However, ~35% suffer long-term mobility impairment following surgery. This may be in part due to muscle inflammation susceptibility (MuIS+), an overt pro-inflammatory pathology localized to skeletal muscle surrounding the diseased joint, present in some TKA/THA patients. PURPOSE: We are interrogating the hypotheses that a) MuIS+/- status will result in a differential perioperative expression profile that may partially explain low functional outcomes, and b) resistance training rehabilitation will more effectively overcome MuIS+ status than usual care for successful recovery post-surgery. METHODS: Muscle, serum, and functional data were leveraged from our ongoing two-site, randomized, controlled trial (N = 75 randomized). Participants were dichotomized based on surgical (SX) muscle gene expression of TNFRSF1A (TNFαR). MuIS+/- samples were probed for transcript expression and indices of skeletal muscle integrity. Preliminary perioperative comparisons were made using two-tailed T-tests; alpha P < 0.05. Preliminary miRNA-seq data were analyzed using Partek Flow; differentially expressed (DE) miRNAs were defined as Fold change (FC) ≥ 1.5 and P ≤ 0.05. RESULTS: 70 participants (27 M/43F; mean age 62 ± 9 yrs; mean BMI 31.3 ± 4.9 kg/m2) undergoing THA/TKA were clustered as MuIS+ (n = 24) or MuIS- (n = 46). MuIS+ muscle exhibited significantly higher pro-inflammatory (IL-6R) and catabolic (TRIM63) gene expression (P = 0.0001 and 0.03, respectively) compared to MuIS-. Further, significantly lower skeletal muscle integrity exists on the SX vs non-SX limb, illustrated by 20% higher fibrosis (P = 0.0003), and 3.5% lower thigh muscle mass (P = 0.005). Preliminary serum miRNA-seq (for N = 9) indicate 193 DE miRNAs (P ≤ 0.05, FC ≥ 1.5) following the intervention. CONCLUSIONS: Preliminary results suggest MuIS+ patients exhibit more inflammation and catabolic signaling in skeletal muscle of the SX limb, accompanied by decreased skeletal muscle integrity. This highlights the profound impact of MuIS+ status and emphasizes the potential value of perioperative MuIS assessment to inform optimal post-surgical care. Funding: T32HD071866, R01HD084124