A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis

Wang, Xiaofang; Ma, Yufei; Chen, Jie; Liu, Yujiao; Liu, Guangliang; Wang, Pengtao; Wang, Bo; Taketo, Makoto Mark; Bellido, Teresita; Tu, Xiaolin

doi:10.1016/j.bioactmat.2022.07.017

Cited by 13 publications

(14 citation statements)

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“…In our laboratory, we found that Wnt-activated osteocytes may affect bone formation by influencing surrounding skeletal cells through paracrine signaling, and specific data showed that Wnt-activated osteocytes promote bone formation, bone resorption [ 15 ], and stem cell proliferation. These findings have translational applications [ 21 , 31 , 32 ] and will be beneficial for BTE. We found that C91 effectively prevented the degradation of β-catenin in the cytoplasm of MLO-Y4 osteocytes and mediated β-catenin entry into the nucleus, thereby significantly increasing the expression of Wnt target genes.…”

Section: Discussionmentioning

confidence: 99%

“…However, the development of the bionic microenvironment is a challenge for the entire industry. In the early stages of our research, we found that the bone cell acellular matrix that was activated by Wnt signaling via gene manipulation accelerated the repair of critical-sized parietal bone defects by promoting osteoblast formation, angiogenesis, and neurogenesis [ 21 ]. Moreover, GelMA/PCL scaffolds containing ST2 cells pretreated with Wnt3a can effectively enhance the osteogenic and angiogenic activities of bone repair biomaterials in vitro and in vivo [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…The 3D modules were cultured in a growth medium for a week, and then bone nodule formation was induced in osteogenic medium containing 0.1 mM dexamethasone, 10 mM β-glycerophosphate disodium salt solution, and 50 μg/mL L-ascorbic acid for 14 days. Matrix mineralization was analyzed by alizarin red S staining as reported [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…Then, stable β-catenin accumulates in the cell nucleus and binds to the TCF/LEF transcription factors, which in turn activates target gene expression [ 19 , 20 ]. Previous studies have found that in vivo activation of Wnt signaling in osteocytes regulates bone formation and bone resorption, which enables bone metabolism [ 15 ] and promotes vascular and neural differentiation [ 21 ]. To replace gene editing for clinical applications, our team focuses on finding small molecule drugs that can stably activate signaling pathways and on developing safe and effective bone regeneration and repair solutions.…”

Section: Introductionmentioning

confidence: 99%

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CHIR99021-Treated Osteocytes with Wnt Activation in 3D-Printed Module Form an Osteogenic Microenvironment for Enhanced Osteogenesis and Vasculogenesis

Luo

Liu

Wang

et al. 2023

IJMS

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Finding a bone implant that has high bioactivity that can safely drive stem cell differentiation and simulate a real in vivo microenvironment is a challenge for bone tissue engineering. Osteocytes significantly regulate bone cell fate, and Wnt-activated osteocytes can reversely regulate bone formation by regulating bone anabolism, which may improve the biological activity of bone implants. To achieve a safe application, we used the Wnt agonist CHIR99021 (C91) to treat MLO-Y4 for 24 h, in a co-culture with ST2 for 3 days after withdrawal. We found that the expression of Runx2 and Osx increased, promoted osteogenic differentiation, and inhibited adipogenic differentiation in the ST2 cells, and these effects were eliminated by the triptonide. Therefore, we hypothesized that C91-treated osteocytes form an osteogenic microenvironment (COOME). Subsequently, we constructed a bio-instructive 3D printing system to verify the function of COOME in 3D modules that mimic the in vivo environment. Within PCI3D, COOME increased the survival and proliferation rates to as high as 92% after 7 days and promoted ST2 cell differentiation and mineralization. Simultaneously, we found that the COOME-conditioned medium also had the same effects. Therefore, COOME promotes ST2 cell osteogenic differentiation both directly and indirectly. It also promotes HUVEC migration and tube formation, which can be explained by the high expression of Vegf. Altogether, these results indicate that COOME, combined with our independently developed 3D printing system, can overcome the poor cell survival and bioactivity of orthopedic implants and provide a new method for clinical bone defect repair.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CHIR99021-Treated Osteocytes with Wnt Activation in 3D-Printed Module Form an Osteogenic Microenvironment for Enhanced Osteogenesis and Vasculogenesis

Luo

Liu

Wang

et al. 2023

IJMS

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“…It can not only provide a three-dimensional scaffold structure for tissue-regenerating cells but also regulate the behavior of these cells [ 17 ], including cell morphology, cell adhesion, cell proliferation, cell migration, cell differentiation and apoptosis. In addition, it can induce the proliferation and differentiation of stem cells in the host body and regulate cell signaling pathways and gene expression [ 18 ] through mechanical perception or receptor-mediated regulation. There are two types of application strategies used for a dECM.…”

Section: Introductionmentioning

confidence: 99%

Treated Dentin Matrix in Tissue Regeneration: Recent Advances

Zhang

Guo

2022

Pharmaceutics

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Tissue engineering is a new therapeutic strategy used to repair serious damage caused by trauma, a tumor or other major diseases, either for vital organs or tissues sited in the oral cavity. Scaffold materials are an indispensable part of this. As an extracellular-matrix-based bio-material, treated dentin matrixes have become promising tissue engineering scaffolds due to their unique natural structure, astonishing biological induction activity and benign bio-compatibility. Furthermore, it is important to note that besides its high bio-activity, a treated dentin matrix can also serve as a carrier and release controller for drug molecules and bio-active agents to contribute to tissue regeneration and immunomodulation processes. This paper describes the research advances of treated dentin matrixes in tissue regeneration from the aspects of its vital properties, biologically inductive abilities and application explorations. Furthermore, we present the concerning challenges of signaling mechanisms, source extension, individualized 3D printing and drug delivery system construction during our investigation into the treated dentin matrix. This paper is expected to provide a reference for further research on treated dentin matrixes in tissue regeneration and better promote the development of relevant disease treatment approaches.

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The decrease in zinc‐finger E‐box‐binding homeobox‐1 could accelerate steroid‐induced osteonecrosis of the femoral head by repressing type‐H vessel formation via Wnt/β‐catenin pathway

Zhang,

Cai,

Liang

et al. 2024

Anim Models and Exp Med

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BackgroundZinc‐finger E‐box‐binding homeobox‐1 (ZEB1) is predominantly found in type‐H vessels. However, the roles of ZEB1 and type‐H vessels in steroid‐induced osteonecrosis of the femoral head (SONFH) are unclear.MethodsHuman femoral heads were collected to detect the expression of ZEB1 and the levels of type‐H vessels. Then, the SONFH model was developed by injecting C57BL/6 mice with lipopolysaccharide and methylprednisolone. Micro‐computed tomography, angiography, double calcein labeling, immunofluorescence, immunohistochemistry, quantitative real‐time polymerase chain reaction, and Western blotting were performed to detect the expression of ZEB1, the Wnt/β‐catenin pathway, type‐H vessels, and the extent to which ZEB1 mediates angiogenesis and osteogenesis. Human umbilical vein endothelial cells were also used to explore the relationship between ZEB1 and the Wnt/β‐catenin pathway.ResultsWe found that ZEB1 expression and the formation of type‐H vessels decreased in SONFH patients and in a mouse model. The number of vascular endothelial growth factors in the femoral heads also decreased. Moreover, the bone mineral density, trabecular number, mineral apposition rate, and expression of genes related to osteogenesis decreased. After ZEB1 knockdown, angiogenesis and osteogenesis decreased. However, the numbers of type‐H vessels and the extent of angiogenesis and osteogenesis improved after activation of the Wnt/β‐catenin pathway.ConclusionsThe ZEB1 expression decreased in SONFH, causing a decrease in type‐H vessel, and it mediated angiogenesis and osteogenesis by regulating the Wnt/β‐catenin pathway, ultimately accelerating the process of SONFH.

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A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis

Cited by 13 publications

References 98 publications

CHIR99021-Treated Osteocytes with Wnt Activation in 3D-Printed Module Form an Osteogenic Microenvironment for Enhanced Osteogenesis and Vasculogenesis

CHIR99021-Treated Osteocytes with Wnt Activation in 3D-Printed Module Form an Osteogenic Microenvironment for Enhanced Osteogenesis and Vasculogenesis

Treated Dentin Matrix in Tissue Regeneration: Recent Advances

The decrease in zinc‐finger E‐box‐binding homeobox‐1 could accelerate steroid‐induced osteonecrosis of the femoral head by repressing type‐H vessel formation via Wnt/β‐catenin pathway

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