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OBJECTIVE The aims of the study were to assess the anti-inflammatory properties of platelet-rich plasma (PRP) and investigate its regenerative potential in osteoarthritic (OA) human chondrocytes. We hypothesized that PRP can modulate the inflammatory response and stimulate cartilage regeneration. DESIGN Primary human chondrocytes from OA knees were treated with manually prepared PRP, after which cell migration and proliferation were assessed. Next, tumor necrosis factor-α-stimulated chondrocytes were treated with a range of concentrations of PRP. Expression of genes involved in inflammation and chondrogenesis was determined by real-time polymerase chain reaction. In addition, chondrocytes were cultured in PRP gels and fibrin gels consisting of increasing concentrations of PRP. The production of cartilage extracellular matrix (ECM) was assessed. Deposition and release of glycosaminoglycans (GAG) and collagen was quantitatively determined and visualized by (immuno)histochemistry. Proliferation was assessed by quantitative measurement of DNA. RESULTS Both migration and the inflammatory response were altered by PRP, while proliferation was stimulated. Expression of chondrogenic markers COL2A1 and ACAN was downregulated by PRP, independent of PRP concentration. Chondrocytes cultured in PRP gel for 28 days proliferated significantly more when compared with chondrocytes cultured in fibrin gels. This effect was dose dependent. Significantly less GAGs and collagen were produced by chondrocytes cultured in PRP gels when compared with fibrin gels. This was qualitatively confirmed by histology. CONCLUSIONS PRP stimulated chondrocyte proliferation, but not migration. Also, production of cartilage ECM was strongly downregulated by PRP. Furthermore, PRP did not act anti-inflammatory on chondrocytes in an in vitro inflammation model.