Research progress on the role of CD14 in osteoarthritis.

Osteoarthritis (OA) is a complex degenerative disease centered on inflammation and involving multi-cellular cooperation, with a continuously rising global burden. Current therapeutic measures mainly focus on symptom relief, slowing progression, and end-stage joint arthroplasty; no disease-modifying or reversal agent is yet available, underscoring the urgent need to dissect the inflammatory driving mechanisms and identify effective intervention targets. As a pattern recognition receptor, CD14 is highly expressed on synovial macrophages in the OA microenvironment. It recognizes endogenous damage-associated molecular patterns, driving pro-inflammatory responses through both TLR4-dependent (MyD88/NF-κB) and TLR4-independent (NLRP3 inflammasome) pathways. Recent studies have accumulated substantial evidence; clinical samples and animal models consistently show that CD14 deficiency or blockade reduces cartilage damage, synovitis, and pain, while soluble CD14 (sCD14) levels positively correlate with inflammatory cytokines and clinical symptoms, indicating its important role in OA pathogenesis and supporting its value as a biomarker and therapeutic target. This review aims to integrate current evidence, clarify the central pro-inflammatory role of CD14 in OA, and provide a theoretical basis for future precision targeted therapies and biomarker-driven clinical trial designs, thereby advancing the development of diagnostic and therapeutic strategies for OA.