A kinetic-based framework for the selection of in vitro osteoarthritis models: integrating temporal dynamics of...

In vitro osteoarthritis (OA) models are widely used for mechanistic studies. However, inconsistencies in induction protocols limit reproducibility and translational relevance. A systematic comparison of inflammatory inducers based on their temporal dynamics remains elusive. A systematic literature search was conducted across PubMed, Web of Science, and Scopus to identify the most commonly used inflammatory inducers in vitro OA models. The prevalence of each inducer was quantified. In addition, a qualitative mechanistic synthesis was performed by integrating representative studies reporting temporal molecular profiles to construct conceptual kinetic patterns. Based on this synthesis, a kinetic-based framework was developed to compare inducer-specific temporal characteristics. Interleukin-1β (IL-1β) was the most frequently used inducer (62.12%), followed by lipopolysaccharide (LPS, 9.60%) and tumor necrosis factor-α (TNF-α, 7.58%). Temporal synthesis suggested a biphasic enzymatic response characterized by early ADAMTS-5 induction (approximately 6-12 h) and subsequent MMP-13 elevation (24-48 h). IL-1β was associated with sustained signaling activation and pronounced transitions between ferroptosis-related and apoptotic-related markers. In contrast, TNF-α induced rapid but transient early-phase responses, whereas LPS exhibited a delayed yet persistent low-grade inflammatory profile. The selection of inflammatory inducers should be aligned with specific experimental objectives. IL-1β is suitable for modeling sustained catabolic activity and cell death transitions, TNF-α for early-stage inflammatory responses, and LPS for chronic low-grade inflammation. This kinetic-based framework may improve model selection and enhance the translational relevance of in vitro OA studies, although further experimental validation is required.