AdipoRon reduces TGFß1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFß1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFß1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

New Ceramic Heads With Titanium Sleeves on Retained Femoral Components: Results of Over 500 Revision Total Hip Arthroplasties.

BACKGROUND: Ceramic heads are frequently combined with titanium sleeves in revision total hip arthroplasties (THAs), ostensibly to protect the ceramic head from existing damage to the retained trunnion. Although widely adopted, data on the performance and safety of this construct are minimal. The purpose of this study was to describe implant survivorships, radiographic results, and clinical outcomes of patients who underwent revision THA with a ceramic head and titanium sleeve on a retained femoral component. METHODS: We identified 516 revision THAs with femoral component retention (328 acetabular-only revisions and 188 bearing surface exchanges) treated with a new ceramic head and titanium sleeve between 2000 and 2020. Mean age at revision was 64 years, 56% were women, and mean body mass index was 30. The indications for revision THA were adverse local tissue reaction (25%), acetabular loosening (24%), dislocation (17%), infection (5%), and other (29%). Kaplan-Meier survivorships were analyzed, radiographs reviewed, and Harris Hip Scores evaluated. Mean follow-up was 4 years (range, 2 to 10). RESULTS: There were no reoperations or failures for ceramic head fracture, taper corrosion, or head/sleeve disengagement. The 10-year survivorship free of any re-revision was 85%. Indications for the 57 re-revisions included dislocation (33), infection (13), acetabular component loosening (7), periprosthetic fracture (2), psoas impingement (1), and sciatic nerve irritation (1). The 10-year survivorship free of any reoperation was 82%. There were an additional 14 reoperations. Radiographically, 1.9% had progressive femoral radiolucent lines, and 4.7% had progressive acetabular radiolucent lines. Mean Harris Hip Score was 81 at 2 years. CONCLUSIONS: New ceramic heads with titanium sleeves in revision THAs with retained femoral components were durable and reliable with no cases of ceramic head fracture or taper complications at mean 4-year follow-up, including those revised for adverse local tissue reaction. LEVEL OF EVIDENCE: IV.