Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype

Marjolein M. J. Caron, Ellen G. J. Ripmeester, Guus van den Akker, Nina K. A. P. Wijnands, Jessica Steijns, Don A. M. Surtel, Andy Cremers, Pieter J. Emans, Lodewijk W. van Rhijn, Tim J. M. Welting*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

Treatment of osteoarthritis (OA) is mainly symptomatic by alleviating pain to postpone total joint replacement. Bone morphogenetic protein 7 (BMP7) is a candidate morphogen for experimental OA treatment that favorably alters the chondrocyte and cartilage phenotype. Intra-articular delivery and sustained release of a recombinant growth factor for treating OA are challenging, whereas the use of peptide technology potentially circumvents many of these challenges. In this study, we screened a high-resolution BMP7 peptide library and discovered several overlapping peptide sequences from two regions in BMP7 with nanomolar bioactivity that attenuated the pathological OA chondrocyte phenotype. A single exposure of OA chondrocytes to peptides p[63-82] and p[113-132] ameliorated the OA chondrocyte phenotype for up to 8 days, and peptides were bioactive on chondrocytes in OA synovial fluid. Peptides p[63-82] and p[113-132] required NKX3-2 for their bioactivity on chondrocytes and provoke changes in SMAD signaling activity. The bioactivity of p[63-82] depended on specific evolutionary conserved sequence elements common to BMP family members. Intra-articular injection of a rat medial meniscal tear (MMT) model with peptide p[63-82] attenuated cartilage degeneration. Together, this study identified two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA.

Original languageEnglish
Pages (from-to)247-261
Number of pages15
JournalMolecular Therapy - Methods and Clinical Development
Volume21
DOIs
Publication statusPublished - 11 Jun 2021

Keywords

  • GENE-EXPRESSION
  • SYNOVIAL-FLUID
  • CHONDROGENIC DIFFERENTIATION
  • HYPERTROPHIC DIFFERENTIATION
  • ARTICULAR CHONDROCYTES
  • CARTILAGE REPAIR
  • PROGENITOR CELLS
  • PROGRESSION
  • BMP7
  • RAT

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