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

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. © 2021 The Authors.

Citation

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. Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype. Molecular therapy. Methods & clinical development. 2021 Jun 11;21:247-261

PMID: 33850953

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