The aim of this review is to provide an updated review of the epigenetic factors involved in the onset and development of osteoarthritis (OA). OA is a prevalent degenerative joint disease characterized by chronic inflammation, ectopic bone formation within the joint, and physical and proteolytic cartilage degradation which result in chronic pain and loss of mobility. At present, no disease-modifying therapeutics exist for the prevention or treatment of the disease. Research has identified several OA risk factors including mechanical stressors, physical activity, obesity, traumatic joint injury, genetic predisposition, and age. Recently, there has been increased interest in identifying epigenetic factors involved in the pathogenesis of OA. In this review, we detail several of these epigenetic modifications with known functions in the onset and progression of the disease. We also review current therapeutics targeting aberrant epigenetic regulation as potential options for preventive or therapeutic treatment.

Complex Lymphatic Anomalies (CLA) are lymphatic malformations with idiopathic bone and soft tissue involvement. The extent of the abnormal lymphatic presentation and boney invasion varies between subtypes of CLA. The etiology of these diseases has proven to be extremely elusive due to their rarity and irregular progression. In this review, we compiled literature on each of the four primary CLA subtypes and discuss their clinical presentation, lymphatic invasion, osseous profile, and regulatory pathways associated with abnormal bone loss caused by the lymphatic invasion. We highlight key proliferation and differentiation pathways shared between lymphatics and bone and how these systems may interact with each other to stimulate lymphangiogenesis and cause bone loss.

Complex lymphatic anomalies (CLAs) are a set of rare diseases with unique osteopathic profiles. Recent efforts have identified how lymphatic-specific somatic activating mutations can induce abnormal lymphatic formations that are capable of invading bone and inducing bone resorption. The abnormal bone resorption in CLA patients has been linked to overactive osteoclasts in areas with lymphatic invasions. Despite these findings, the mechanism associated with progressive bone loss in CLAs remains to be elucidated. In order to determine the role of osteoblasts in CLAs, we sought to assess osteoblast differentiation and bone formation when exposed to the lymphatic endothelial cell secretome. When treated with lymphatic endothelial cell conditioned medium (L-CM), osteoblasts exhibited a significant decrease in proliferation, differentiation, and function. Additionally, L-CM treatment also inhibited bone formation through a neonatal calvaria explant culture. These findings are the first to reveal how osteoblasts may be actively suppressed during bone lymphatic invasion in CLAs.

Background: Total knee arthroplasty is a widely endorsed surgical intervention, extensively recognized within the orthopedic field for its efficacy in significantly reducing pain and enhancing overall mobility in patients suffering from advanced stages of osteoarthritis. Despite a general consensus on the core procedural steps, the rapid advancements in implant technology and the nuanced techniques in knee reconstruction have inevitably introduced subtle variations in surgical approaches. These variations often emerge due to individual surgeon preferences, their unique expertise, and comfort levels with specific techniques. Anterior knee pain, however, remains a frequent postoperative complication, likely attributed to the extensive and complex innervation of the patella. To address this challenge, some surgeons have adopted patellar denervation, hypothesizing that by reducing nerve signaling from the patellar region, patients may experience a measurable decrease in pain. Methods: A systematic search was performed to include eight recent level I studies to analyze this issue. Results: Of the eight reviews, there were four strong studies that concluded patellar denervation helps decrease anterior knee pain in the acute period, but this may not last long term. The other four papers did not show a difference in anterior knee pain after denervation. Conclusions: This review synthesizes and critically analyzes the current body of literature, aiming to provide clinicians with evidence-based insights into the potential benefits and limitations of incorporating patellar denervation into their surgical especially during the acute post-operative period.