Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Though various animal models are existing, the translation of these models into clinics remains difficult due to species differences. To advance the clinical relevance of research data, a preclinical OA model with human samples is indispensable.
In this study, an ex vivo inflammatory OA model was induced using explants from human OA femoral head. Effects of treatment with different concentrations of IL-1β and TNF-α were compared after 3- and 7-day culture duration. The samples were assessed histologically (n = 3/group), biochemically (n = 6-11/group), and transcriptionally (n = 6-8/group).
In the inflammatory OA groups, the gene expression levels of cartilage catabolism (MMP1, MMP3), and inflammation (IL-6, IL-8) markers were significantly upregulated, while the anabolic genes (COL2, ACAN, PRG4) were downregulated compared with the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in conditioned medium was also upregulated in the inflammatory OA groups. The Safranin O/Fast Green staining showed that the degradation of proteoglycan in the superficial zone cartilage presented a positive correlation with culture duration and concentration of IL-1β and TNF-α. Cell viability in the cartilage tissue was > 85% and comparable among all groups. For establishment of human osteochondral explant inflammatory OA model, 1 ng/mL IL-1β + TNF-α were enough to induce a mild inflammatory OA condition; 5 ng/mL IL-1β + TNF-α induced a more profound inflammatory and catabolic effect; 10 ng/mL IL-1β + TNF-α showed a similar effect as 5 ng/mL.
The results indicate that an ex vivo OA model of inflammation and degeneration was successfully established using osteochondral explants from human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA, and to screen new drugs for its treatment.