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SAP15 (Synthetic anti-inflammatory peptide 15) is a synthetic anti-inflammatory peptide consisting of 15 amino acids designed from human beta-defensin 3. SAP15 has the ability to penetrate cells and is able to induce downregulation of intracellular inflammation. SAP15 inhibits inflammation by inhibiting the phosphorylation of HDAC5 and thereby reducing the phosphorylation of NF-κB p65. In LPS-induced macrophages, SAP15 inhibits HDAC5 and NF-κB p65 phosphorylation. In addition, SAP15 treatment increased the expression of aggrecan and type II collagen and decreased the expression of osteocalcin in LPS-induced chondrocytes. SAP15 can be used in the study of inflammation regulation and anti-inflammatory therapy of biomaterials.