Discovery of bone morphogenetic protein 7-derived peptide sequences that attenuate the human osteoarthritic chondrocyte phenotype.
BMP7
chondrocyte phenotype
hypertrophy
osteoarthritis
peptides
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
11 Jun 2021
11 Jun 2021
Historique:
received:
28
11
2020
accepted:
09
03
2021
entrez:
14
4
2021
pubmed:
15
4
2021
medline:
15
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33850953
doi: 10.1016/j.omtm.2021.03.009
pii: S2329-0501(21)00049-8
pmc: PMC8022858
doi:
Types de publication
Journal Article
Langues
eng
Pagination
247-261Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The study sponsors had no involvement in study design, collection, analysis, and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. M.M.J.C. and T.J.M.W. are inventors on patents WO2017178251 and WO2017178253 (owned by Chondropeptix). P.J.E., L.W.v.R., and T.J.M.W. are shareholders in Chondropeptix and are CMO, CDO, and CSO of Chondropeptix, respectively. The other authors declare no competing interests.
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