Functionalization of biomaterials with small osteoinductive moieties

The aim of this study was to characterize the physicochemical properties of bacterial cellulose (BC) membranes functionalized with osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP[10–14], and to evaluate in vitro osteoinductive potential in early osteogenesis, besides, to evaluate cytotoxic, genotoxic and/or mutagenic effects. Peptide incorporation into the BC membranes did not change the morphology of BC nanofibers and BC crystallinity pattern. The characterization was complemented by Raman scattering, swelling ratio and mechanical tests. In vitro assays demonstrated no cytotoxic, genotoxic or mutagenic effects for any of the studied BC membranes. Culture with osteogenic cells revealed no difference in cell morphology among all the membranes tested. Cell viability/proliferation, total protein content, alkaline phosphatase activity and mineralization assays indicated that BC-OGP membranes enabled the highest development of the osteoblastic phenotype in vitro. In conclusion, the negative results of cytotoxicity, genotoxicity and mutagenicity indicated that all the membranes can be employed for medical supplies, mainly in bone tissue engineering/regeneration, due to their osteoinductive properties.

Characterization and in vitro evaluation of bacterial cellulose membranes functionalized with osteogenic growth peptide for bone tissue engineering

Materials-based nanotherapeutics for injured and diseased bone

Carcinoma-associated fibroblasts (CAFs) consist of heterogeneous subpopulations that play a critical role in the dynamics of the tumor microenvironment. The extracellular signals of CAFs have been attributed to the extracellular matrix, cytokines, cell surface checkpoints, and exosomes. In the present study, it is demonstrated that the CD10 transmembrane hydrolase expressed on a subset of CAFs supports tumor stemness and induces chemoresistance. Mechanistically, CD10 degenerates an antitumoral peptide termed osteogenic growth peptide (OGP). OGP restrains the expression of rate-limiting desaturase SCD1 and inhibits lipid desaturation, which is required for cancer stem cells (CSCs). Targeting CD10 significantly improves the efficacy of chemotherapy in vivo. Clinically, CD10-OGP signals are associated with the response to neoadjuvant chemotherapy in patients with breast cancer. The collective data suggest that a nexus between the niche and lipid metabolism in CSCs is a promising therapeutic target for breast cancer.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202101848

A CD10-OGP Membrane Peptolytic Signaling Axis in Fibroblasts Regulates Lipid Metabolism of Cancer Stem Cells via SCD1.

Raquel Mantuaneli Scarel-Caminaga a, , Sybele Saska , Leonardo Pereira Franchi , Raquel A. Santos , Ana Maria Minarelli Gaspar , Ticiana S.O. Capote , Sidney Jose Lima Ribeiro , Younes Messaddeq , Reinaldo Marchetto , Catarina S. Takahashi c,d a School of Dentistry at Araraquara, Sao Paulo State University, UNESP, Department of Morphology. Rua Humaita, 1680, AraraquaraSP, Brazil. Institute of Chemistry, Sao Paulo State University, UNESP. Rua Francisco DegniAraraquaraSP, Brazil. c Faculty of Medicine of Ribeirao Preto, Sao Paulo University, USP, Department of Genetic. Bloco G. Av. Bandeirantes, 3900, Ribeirao Preto, SP, Brazil. d Faculty of Phylosophy, Sciences and Lyrics, Sao Paulo University, USP, Department of Biology. Av. Bandeirantes, 3900, Ribeirao Preto, SP, Brazil. e University of Franca, UNIFRAN. Avenida Dr. Armando Salles OliveiraFranca-SP, Brazil.

Nanocomposites based on bacterial cellulose in combination with osteogenic growth peptide for bone repair: cytotoxic, genotoxic and mutagenic evaluations

Osteogenic growth peptide (OGP) was characterized in regenerating bone marrow, which can increase osteogenesis and hematopoiesis. The carboxy-terminal pentapeptide is a naturally occurring human and murine mitogen equipotent to OGP. In this study, we evaluated the potential role of OGP10-14 in regulation of hematopoiesis in human hematopoietic stem cells and animal model. Our results showed CD34+ stem cells from umbilical cord blood (UBC) were significantly increased in OGP10-14 treated samples, which is nearly equivalent to the results obtained from the combinations of IL3, IL11, G-CSF, and EPO group. OGP10-14 can also stimulate the differentiation of stem cells from bone marrow at the level of noncommitted progenitor stem cells, thus increasing the number of reconstituted red and white cells as well as platelets after injected i.m. everyday continuing for 5 days in hematopoietic function damage mice comparing with the OGP-untreated group. These data implicate that the role of OGP10-14 regulating hematopoiesis is in the early stage of the whole hematopoietic growth factors (HGFs) regulating network, just like the position of interleukin 13 in the hematopoiesis network.

C-terminal pentapeptide of osteogenic growth peptide regulates hematopoiesis in early stage.

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C-terminal pentapeptide of osteogenic growth peptide regulates hematopoiesis in early stage.