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

Autor:	Caron MMJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands., Ripmeester EGJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands., van den Akker G; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands., Wijnands NKAP; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands., Steijns J; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands., Surtel DAM; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands., Cremers A; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands., Emans PJ; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands.; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands., van Rhijn LW; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands.; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands., Welting TJM; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands.; Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2021 Mar 17; Vol. 21, pp. 247-261. Date of Electronic Publication: 2021 Mar 17 (Print Publication: 2021).
DOI:	10.1016/j.omtm.2021.03.009
Abstrakt:	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. Competing Interests: 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. (© 2021 The Authors.)
Databáze:	MEDLINE
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