New Clues to the Challenge of Knee Arthrofibrosis: From Molecules to Therapies

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Knee arthrofibrosis (AF) is a debilitating complication after total knee arthroplasty. AF is characterized by formation of fibrotic adhesions, loss of joint mobility, and pain. With osteoarthritis prevalence and associated total knee arthroplasties projected to rise sharply, AF is becoming increasingly prevalent, yet its pathogenesis remains poorly understood and no effective treatments exist. Like other fibrotic diseases, knee AF is a multifactorial disease that exhibits TGFβ1-driven myofibroblast transformation and excessive collagen deposition. However, knee AF also displays unique features, including rapid disease development and the establishment of a highly fibrotic mass rather than fibrotic tissue infiltration. Our integrative research approach uses human patient fibroblasts, multiomics profiling, and in vivo animal models to dissect disease mechanisms and identify therapeutic targets. Our work suggests altered adipogenic cell differentiation in the knee and epigenetic pathways controlling myofibroblastogenesis to be involved in AF development. Anti-inflammatory interventions with ketotifen and celecoxib reduce knee AF in vivo, indicating a contributory role of inflammation as well. Together, our novel findings elucidate causal and mechanistic drivers of AF and define this disease as an adipose-depleted fibrotic disorder driven by aberrant differentiation and epigenetic

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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