Enhanced BMP signaling leads to enlarged nasal cartilage formation in mice

Yamaguchi, Hiroyuki; Swaminathan, Sowmya; Mishina, Yuji; Komatsu, Yoshihiro

doi:10.1016/j.bbrc.2023.08.053

Cited by 2 publications

(1 citation statement)

References 34 publications

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“…The 3D bioprinted constructs demonstrated long-term cell viability and activation of the pro-chondrogenic Wnt/β-catenin signaling cascade . There are also reports of successful chondrogenesis poststimulation of BMSCs with an array of growth factors like transforming growth factor-β (TGFβ), , bone morphogenetic protein (BMP), , platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF) owing to their high proliferation ability, ease of availability, and the ability to be differentiated into multiple tissue types. , Moreover, the majority of the research works focused on hyaline cartilage formation in vitro under normal chondrogenic culture conditions rather than evaluating the maintenance of stable articular cartilage phenotype in vitro under OA-mimicking microenvironment. As a result, a hypertrophic phenotypic drift occurs in the implanted cartilage grafts …”

Section: Introductionmentioning

confidence: 99%

Covalent Conjugation of Small Molecule Inhibitors and Growth Factors to a Silk Fibroin-Derived Bioink to Develop Phenotypically Stable 3D Bioprinted Cartilage

Majumder,

Roy,

Doenges

et al. 2024

ACS Appl. Mater. Interfaces

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Implantation of a phenotypically stable cartilage graft could represent a viable approach for repairing osteoarthritic (OA) cartilage lesions. In the present study, we investigated the effects of modulating the bone morphogenetic protein (BMP), transforming growth factor beta (TGFβ), and interleukin-1 (IL-1) signaling cascades in human bone marrow stromal cell (hBMSC)encapsulated silk fibroin gelatin (SF-G) bioink. The selected small molecules LDN193189, TGFβ3, and IL1 receptor antagonist (IL1Ra) are covalently conjugated to SF-G biomaterial to ensure sustained release, increased bioavailability, and printability, confirmed by ATR-FTIR, release kinetics, and rheological analyses. The 3D bioprinted constructs with chondrogenically differentiated hBMSCs were incubated in an OA-inducing medium for 14 days and assessed through a detailed qPCR, immunofluorescence, and biochemical analyses. Despite substantial heterogeneity in the observations among the donors, the IL1Ra molecule illustrated the maximum efficiency in enhancing the expression of articular cartilage components, reducing the expression of hypertrophic markers (re-validated by the GeneMANIA tool), as well as reducing the production of inflammatory molecules by the hBMSCs. Therefore, this study demonstrated a novel strategy to develop a chemically decorated, printable and biomimetic SF-G bioink to produce hyaline cartilage grafts resistant to acquiring OA traits that can be used for the treatment of degenerated cartilage lesions.

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Section: Introductionmentioning

confidence: 99%

Covalent Conjugation of Small Molecule Inhibitors and Growth Factors to a Silk Fibroin-Derived Bioink to Develop Phenotypically Stable 3D Bioprinted Cartilage

Majumder,

Roy,

Doenges

et al. 2024

ACS Appl. Mater. Interfaces

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Distribution of Immunomodulation, Protection and Regeneration Factors in Cleft-Affected Bone and Cartilage

Vaivads,

Pilmane

2024

Diagnostics

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Background: Craniofacial clefts can form a significant defect within bone and cartilage, which can negatively affect tissue homeostasis and the remodeling process. Multiple proteins can affect supportive tissue growth, while also regulating local immune response and tissue protection. Some of these factors, like galectin-10 (Gal-10), nuclear factor kappa-light-chain-enhancer of activated B cells protein 65 (NF-κB p65), heat shock protein 60 (HSP60) and 70 (HSP70) and cathelicidin (LL-37), have not been well studied in cleft-affected supportive tissue, while more known tissue regeneration regulators like type I collagen (Col-I) and bone morphogenetic proteins 2 and 4 (BMP-2/4) have not been assessed jointly with immunomodulation and protective proteins. Information about the presence and interaction of these proteins in cleft-affected supportive tissue could be helpful in developing biomaterials and improving cleft treatment. Methods: Two control groups and two cleft patient groups for bone tissue and cartilage, respectively, were organized with five patients in each group. Immunohistochemistry with the semiquantitative counting method was implemented to determine Gal-10-, NF-κB p65-, HSP60-, HSP70-, LL-37-, Col-I- and BMP-2/4-positive cells within the tissue. Results: Factor-positive cells were identified in each study group. Multiple statistically significant correlations were identified. Conclusions: A significant increase in HSP70-positive chondrocytes in cleft patients could indicate that HSP70 might be reacting to stressors caused by the local tissue defect. A significant increase in Col-I-positive osteocytes in cleft patients might indicate increased bone remodeling and osteocyte activity due to the presence of a cleft. Correlations between factors indicate notable differences in molecular interactions within each group.

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Enhanced BMP signaling leads to enlarged nasal cartilage formation in mice

Cited by 2 publications

References 34 publications

Covalent Conjugation of Small Molecule Inhibitors and Growth Factors to a Silk Fibroin-Derived Bioink to Develop Phenotypically Stable 3D Bioprinted Cartilage

Covalent Conjugation of Small Molecule Inhibitors and Growth Factors to a Silk Fibroin-Derived Bioink to Develop Phenotypically Stable 3D Bioprinted Cartilage

Distribution of Immunomodulation, Protection and Regeneration Factors in Cleft-Affected Bone and Cartilage

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