Engineered synthetic cell penetrating peptide with intracellular anti‐inflammatory bioactivity: An in vitro and in vivo study
Various biomaterials have been used for bone and cartilage regeneration, and inflammation associated with biomaterial implantation is also increased. A 15‐mer synthetic anti‐inflammatory peptide (SAP15) was designed from human β‐defensin 3 to penetrate cells and induce intracellular downregulation o...
Saved in:
Published in | Journal of biomedical materials research. Part A Vol. 109; no. 10; pp. 2001 - 2016 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.10.2021
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Various biomaterials have been used for bone and cartilage regeneration, and inflammation associated with biomaterial implantation is also increased. A 15‐mer synthetic anti‐inflammatory peptide (SAP15) was designed from human β‐defensin 3 to penetrate cells and induce intracellular downregulation of inflammation. The downregulation of inflammation was achieved by the binding of SAP15 to intracellular histone deacetylase (HDAC5). SAP15‐mediated inhibition of inflammation was examined in vitro and in vivo using murine macrophages, human articular chondrocytes, and a collagen‐induced arthritis (CIA) rat model. Surface plasmon resonance and immunoprecipitation assays indicated that SAP15 binds to HDAC5. SAP15 inhibited the lipopolysaccharide (LPS)‐induced phosphorylation of intracellular HDAC5 and NF‐κB p65 in murine macrophages. SAP15 treatment increased aggrecan and type II collagen expression and decreased osteocalcin expression in LPS‐induced chondrocytes. Subcutaneous injection of SAP15‐loaded sodium hyaluronic acid (HA) solution significantly decreased hind paw swelling, joint inflammation, and serum cytokine levels in CIA rats compared with the effects of sodium HA solution alone. The SAP15‐loaded HA group exhibited preservation of cartilage and bone structure in CIA rat joints. Moreover, a more robust anti‐inflammatory effect of the SAP15 loaded HA was observed than that of etanercept (an anti‐tumor necrosis factor‐alpha [TNF‐α] antibody)‐loaded HA. These findings suggest that SAP15 has an anti‐inflammatory effect that is not controlled by sodium HA and is mediated by inhibiting HDAC5, unlike the anti‐inflammatory mechanism of etanercept. These results demonstrate that SAP15 is useful as an inflammatory regulator of biomaterials and can be developed as a therapeutic for the treatment of inflammation. |
---|---|
Bibliography: | Funding information Ministry of Science and ICT, South Korea, Grant/Award Number: NRF‐2017 M3A9B3063635 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1549-3296 1552-4965 |
DOI: | 10.1002/jbm.a.37192 |