Peptide Therapeutics for Osteoarthritis: Osteoimmune Mechanisms, Clinical Evidence, and Priorities for Translation

Osteoarthritis is a heterogeneous whole-joint disorder involving mechanical dysfunction, inflammatory signaling, extracellular matrix degradation, and abnormal subchondral bone remodeling. This narrative review evaluates peptide therapeutics by biological function and translational readiness. We synthesize evidence on immunomodulatory and pro-resolution peptides, growth-factor-derived and mimetic peptides, exploratory soft-tissue repair peptides, extracellular matrix-derived and biomimetic peptides, dietary peptide hydrolysates, and peptide-based delivery systems. Evidence from human osteoarthritis, experimental osteoarthritis, focal osteochondral defects, and broader inflammatory or tissue-repair settings is distinguished. Selected peptides show anti-inflammatory, anti-catabolic, or reparative effects in cell and animal models, but these findings do not establish clinical efficacy. Human studies predominantly examine oral collagen hydrolysates and report formulation-specific improvements in pain or function. Their interpretation is limited by small samples, analysis populations, short follow-up, and reporting quality. Investigational intra-articular peptides provide additional signals, although negative primary endpoints and exploratory structural analyses require caution. No peptide intervention reviewed has established reproducible structural disease modification in human osteoarthritis. Clinical translation requires independently replicated efficacy, adequate safety assessment, reproducible manufacturing, and prospective trials that distinguish symptomatic improvement from structural disease modification.