Characterization Of Muscle Inflammation Susceptibility: A Potential Prognostic Factor For Optimal Post-surgical Rehabilitation

Abstract

BACKGROUND: 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. Previously, we have shown this may be in part due to muscle inflammation susceptibility (MuIS(+)), an overt pro-inflammatory state localized to skeletal muscle surrounding the diseased joint, found in some but not all 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 effective recovery post-surgery. METHODS: Muscle samples were leveraged from our ongoing two-site, randomized, controlled trial (N=84). Participants were dichotomized to MuIS status (+/-) based on surgical (SX) muscle gene expression of Fn14 which drives pro-inflammatory signaling via NFκB. MuIS(+/-) samples were probed for pro-inflammatory gene and protein expression targets, and indices of skeletal muscle function. Preliminary perioperative comparisons were made using two-tailed T-tests; alpha P≤0.05. RESULTS: 84 participants (29M/55F; 62±8yrs; BMI 30.7±5.4kg/m2) undergoing THA/TKA were assessed. Thus far, 37 have been clustered as MuIS(+) (n=14, ~4-fold greater Fn14 mRNA) or MuIS(-) (n=23). SX thigh muscle mass (TMM), quadriceps power and torque were lower (P<0.05) than the contralateral limb (CTR). Additionally, skeletal muscle fibrosis and type II cross-sectional area were greater in the SX leg and MuIS(+) respectively (P<0.05). Tumor necrosis factor-α receptor and IL-6 trended higher in MuIS(+) (P>0.05). Phosphorylated (P)-RPS6 was lower in the SX leg and P-4E-BP1 was significantly lower in MuIS(+) (P>0.05). CONCLUSIONS: Preliminary results suggest patients undergoing TKA/THA exhibit more inflammation on the SX limb, accompanied by lower TMM, torque and power. MuIS(+) leads to greater inflammation and blunted anabolic signaling, highlighting the profound impact of muscle inflammation and emphasizing the potential value in perioperative MuIS assessment to inform optimal post-surgical care. Grant: R01HD084124