2. Academic Validation
  3. A Synthetic Cell-Penetrating Heparin-Binding Peptide Derived from BMP4 with Anti-Inflammatory and Chondrogenic Functions for the Treatment of Arthritis

A Synthetic Cell-Penetrating Heparin-Binding Peptide Derived from BMP4 with Anti-Inflammatory and Chondrogenic Functions for the Treatment of Arthritis

  • Int J Mol Sci. 2020 Jun 15;21(12):4251. doi: 10.3390/ijms21124251.
Da Hyeon Choi 1,  Dongwoo Lee 2,  Beom Soo Jo 2,  Kwang-Sook Park 3,  Kyeong Eun Lee 1,  Ju Kwang Choi 1,  Yoon Jeong Park 2 3,  Jue-Yeon Lee 2,  Yoon Shin Park 1
Affiliations

Affiliations

  • 1 School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Korea.
  • 2 Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), School of Dentistry, Seoul National University, Seoul 03080, Korea.
  • 3 Department of Dental Regenerative Bioengineering and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Korea.
PMID: 32549254 DOI: 10.3390/ijms21124251
Abstract

We report dual therapeutic effects of a synthetic heparin-binding peptide (HBP) corresponding to residues 15-24 of the heparin binding site in BMP4 in a collagen-induced rheumatic arthritis model (CIA) for the first time. The cell penetrating capacity of HBP led to improved cartilage recovery and anti-inflammatory effects via down-regulation of the iNOS-IFNγ-IL6 signaling pathway in inflamed RAW264.7 cells. Both arthritis and paw swelling scores were significantly improved following HBP injection into CIA model mice. Anti-rheumatic effects were accelerated upon combined treatment with Enbrel® and HBP. Serum IFNγ and IL6 concentrations were markedly reduced following intraperitoneal HBP injection in CIA mice. The anti-rheumatic effects of HBP in mice were similar to those of Enbrel®. Furthermore, the combination of Enbrel® and HBP induced similar anti-rheumatic and anti-inflammatory effects as Enbrel®. We further investigated the effect of HBP on damaged chondrocytes in CIA mice. Regenerative capacity of HBP was confirmed based on increased expression of chondrocyte biomarker genes, including aggrecan, Collagen type II and TNFα, in adult human knee chondrocytes. These findings collectively support the utility of our cell-permeable bifunctional HBP with anti-inflammatory and chondrogenic properties as a potential source of therapeutic agents for degenerative inflammatory diseases.

Keywords

Enbrel; anti-inflammatory peptide; cell permeable peptide; collagen-induced arthritis; heparin-binding peptide; inducible nitric oxide; interferon gamma; interleukin-6.

Figures
Products