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Article

In Vitro Chondrogenesis Induction by Short Peptides of the Carboxy-Terminal Domain of Transforming Growth Factor β1

by
Maria Pitou
1,
Eleni Papachristou
1,
Dimitrios Bratsios
2,
Georgia-Maria Kefala
3,
Anastasia S. Tsagkarakou
3,
Demetrios D. Leonidas
3,
Amalia Aggeli
2,
Georgios E. Papadopoulos
3,
Rigini M. Papi
1 and
Theodora Choli-Papadopoulou
1,*
1
Laboratory of Biochemistry, School of Chemistry, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece
2
Laboratory of Biomedical Engineering, School of Chemical Engineering, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece
3
Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, 41500 Larissa, Greece
*
Author to whom correspondence should be addressed.
Biomedicines 2023, 11(12), 3182; https://doi.org/10.3390/biomedicines11123182
Submission received: 17 September 2023 / Revised: 9 November 2023 / Accepted: 14 November 2023 / Published: 29 November 2023
(This article belongs to the Special Issue Biomaterials for Bone Regeneration)
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Abstract

Τransforming growth factor β1 (TGF-β1) comprises a key regulator protein in many cellular processes, including in vivo chondrogenesis. The treatment of human dental pulp stem cells, separately, with Leu83-Ser112 (C-terminal domain of TGF-β1), as well as two very short peptides, namely, 90-YYVGRKPK-97 (peptide 8) and 91-YVGRKP-96 (peptide 6) remarkably enhanced the chondrogenic differentiation capacity in comparison to their full-length mature TGF-β1 counterpart either in monolayer cultures or 3D scaffolds. In 3D scaffolds, the reduction of the elastic modulus and viscous modulus verified the production of different amounts and types of ECM components. Molecular dynamics simulations suggested a mode of the peptides’ binding to the receptor complex TβRII-ALK5 and provided a possible structural explanation for their role in inducing chondrogenesis, along with endogenous TGF-β1. Further experiments clearly verified the aforementioned hypothesis, indicating the signal transduction pathway and the involvement of TβRII-ALK5 receptor complex. Real-time PCR experiments and Western blot analysis showed that peptides favor the ERK1/2 and Smad2 pathways, leading to an articular, extracellular matrix formation, while TGF-β1 also favors the Smad1/5/8 pathway which leads to the expression of the metalloproteinases ADAMTS-5 and MMP13 and, therefore, to a hypertrophic chondrocyte phenotype. Taken together, the two short peptides, and, mainly, peptide 8, could be delivered with a scaffold to induce in vivo chondrogenesis in damaged articular cartilage, constituting, thus, an alternative therapeutic approach for osteoarthritis.
Keywords: transforming growth fβ1; cartilage repair; chondrogenesis; Smad signaling transforming growth fβ1; cartilage repair; chondrogenesis; Smad signaling

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MDPI and ACS Style

Pitou, M.; Papachristou, E.; Bratsios, D.; Kefala, G.-M.; Tsagkarakou, A.S.; Leonidas, D.D.; Aggeli, A.; Papadopoulos, G.E.; Papi, R.M.; Choli-Papadopoulou, T. In Vitro Chondrogenesis Induction by Short Peptides of the Carboxy-Terminal Domain of Transforming Growth Factor β1. Biomedicines 2023, 11, 3182. https://doi.org/10.3390/biomedicines11123182

AMA Style

Pitou M, Papachristou E, Bratsios D, Kefala G-M, Tsagkarakou AS, Leonidas DD, Aggeli A, Papadopoulos GE, Papi RM, Choli-Papadopoulou T. In Vitro Chondrogenesis Induction by Short Peptides of the Carboxy-Terminal Domain of Transforming Growth Factor β1. Biomedicines. 2023; 11(12):3182. https://doi.org/10.3390/biomedicines11123182

Chicago/Turabian Style

Pitou, Maria, Eleni Papachristou, Dimitrios Bratsios, Georgia-Maria Kefala, Anastasia S. Tsagkarakou, Demetrios D. Leonidas, Amalia Aggeli, Georgios E. Papadopoulos, Rigini M. Papi, and Theodora Choli-Papadopoulou. 2023. "In Vitro Chondrogenesis Induction by Short Peptides of the Carboxy-Terminal Domain of Transforming Growth Factor β1" Biomedicines 11, no. 12: 3182. https://doi.org/10.3390/biomedicines11123182

APA Style

Pitou, M., Papachristou, E., Bratsios, D., Kefala, G.-M., Tsagkarakou, A. S., Leonidas, D. D., Aggeli, A., Papadopoulos, G. E., Papi, R. M., & Choli-Papadopoulou, T. (2023). In Vitro Chondrogenesis Induction by Short Peptides of the Carboxy-Terminal Domain of Transforming Growth Factor β1. Biomedicines, 11(12), 3182. https://doi.org/10.3390/biomedicines11123182

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