Osteoarthritis as a Whole-Joint Disease, Part II: Emerging Nociceptive, Metabolic, Senescence, and Regenerative Therapeutic Targets, with Perspectives on Precision Care.

This second part of the review builds on Part I, which focused on current standard-of-care management and structural therapeutic targets within the joint compartment, including cartilage, synovium, and subchondral bone. Here, we examine therapeutic strategies that extend beyond that axis, including peripheral and central pain pathways, systemic metabolic dysfunction and obesity, aging-associated cellular senescence, and contemporary regenerative intra-articular therapies such as platelet-rich plasma, hyaluronic acid, lubricin, and cell-based products. Although several of these approaches have shown encouraging mechanistic or symptomatic signals, consistent and durable clinical success has remained limited.