CRISPR interference-mediated noggin knockdown promotes BMP2-induced osteogenesis and calvarial bone healing

Hsu, Mu‐Nung; Yu, Fu-Jen; Chang, Yu‐Han; Huang, Kai-Lun; Pham, Nam Ngoc; Truong, Vu Anh; Lin, Mingyao; Nguyen, Nuong Thi Kieu; Hwang, Shiaw-Min; Hu, Yu‐Chen

doi:10.1016/j.biomaterials.2020.120094

Cited by 34 publications

(24 citation statements)

References 66 publications

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“…In addition, we demonstrated the nuclear expression of RUNX2 through PASI-stimulated BMP2 and Wnt3a signaling using Noggin and PKF. Noggin interacts with and antagonizes the action of BMP2 [49]. PKF disrupts β-catenin-TCF and inhibits β-catenin-regulated transcription activity [50,51].…”

Section: Discussionmentioning

confidence: 99%

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Park

Lee

Cho

et al. 2021

IJMS

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Paeonia suffruticosa is a magnificent and long-lived woody plant that has traditionally been used to treat various diseases including inflammatory, neurological, cancer, and cardiovascular diseases. In the present study, we demonstrated the biological mechanisms of paeonoside (PASI) isolated from the dried roots of P. suffruticosa in pre-osteoblasts. Herein, we found that PASI has no cytotoxic effects on pre-osteoblasts. Migration assay showed that PASI promoted wound healing and transmigration in osteoblast differentiation. PASI increased early osteoblast differentiation and mineralized nodule formation. In addition, PASI enhanced the expression of Wnt3a and bone morphogenetic protein 2 (BMP2) and activated their downstream molecules, Smad1/5/8 and β-catenin, leading to increases in runt-related transcription factor 2 (RUNX2) expression during osteoblast differentiation. Furthermore, PASI-mediated osteoblast differentiation was attenuated by inhibiting the BMP2 and Wnt3a pathways, which was accompanied by reduction in the expression of RUNX2 in the nucleus. Taken together, our findings provide evidence that PASI enhances osteoblast differentiation and mineralized nodules by regulating RUNX2 expression through the BMP2 and Wnt3a pathways, suggesting a potential role for PASI targeting osteoblasts to treat bone diseases including osteoporosis and periodontitis.

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Section: Discussionmentioning

confidence: 99%

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Park

Lee

Cho

et al. 2021

IJMS

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“…Noggin knockdown led to increased BMP-2 activity within the cranial defects, which accelerated the repair of the lesion compared with defects that received cells transduced with a vector carrying a control shRNA. A recent study explored simultaneous noggin suppression and BMP-2 overexpression in rat adipose-derived stem cells [153]. Cells were co-transduced with baculovirus vectors carrying a BMP-2 gene and a CRISPR interference system to target endogenous noggin and then implanted in rat cranial defects using gelatin as carrier.…”

Section: Cell-based Gene Therapy For Cranial Bone Regenerationmentioning

confidence: 99%

A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration

et al. 2022

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Current cranial repair techniques combine the use of autologous bone grafts and biomaterials. In addition to their association with harvesting morbidity, autografts are often limited by insufficient quantity of bone stock. Biomaterials lead to better outcomes, but their effectiveness is often compromised by the unpredictable lack of integration and structural failure. Bone tissue engineering offers the promising alternative of generating constructs composed of instructive biomaterials including cells or cell-secreted products, which could enhance the outcome of reconstructive treatments. This review focuses on cell-based approaches with potential to regenerate calvarial bone defects, including human studies and preclinical research. Further, we discuss strategies to deliver extracellular matrix, conditioned media and extracellular vesicles derived from cell cultures. Recent advances in 3D printing and bioprinting techniques that appear to be promising for cranial reconstruction are also discussed. Finally, we review cell-based gene therapy approaches, covering both unregulated and regulated gene switches that can create spatiotemporal patterns of transgenic therapeutic molecules. In summary, this review provides an overview of the current developments in cell-based strategies with potential to enhance the surgical armamentarium for regenerating cranial vault defects.

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“…From the perspective of recombinant protein strategies, new technologies have emerged that are still in their infancy but have a high potential in bone regenerative medicine. Particularly noteworthy in this regard, a very recent report from Hsu et al [ 102 ] has exploited the fact that BMP2 is known to induce the expression of its antagonist noggin that self-restricts its bioactivity. Therefore, they proposed that a CRISPRi-based system providing noggin inhibition concurrently to BMP2 overexpression might improve bone healing.…”

Section: Future Perspectivesmentioning

confidence: 99%

Recombinant Proteins-Based Strategies in Bone Tissue Engineering

et al. 2021

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The increase in fracture rates and/or problems associated with missing bones due to accidents or various pathologies generates socio-health problems with a very high impact. Tissue engineering aims to offer some kind of strategy to promote the repair of damaged tissue or its restoration as close as possible to the original tissue. Among the alternatives proposed by this specialty, the development of scaffolds obtained from recombinant proteins is of special importance. Furthermore, science and technology have advanced to obtain recombinant chimera’s proteins. This review aims to offer a synthetic description of the latest and most outstanding advances made with these types of scaffolds, particularly emphasizing the main recombinant proteins that can be used to construct scaffolds in their own right, i.e., not only to impregnate them, but also to make scaffolds from their complex structure, with the purpose of being considered in bone regenerative medicine in the near future.

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CRISPR interference-mediated noggin knockdown promotes BMP2-induced osteogenesis and calvarial bone healing

Cited by 34 publications

References 66 publications

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration

Recombinant Proteins-Based Strategies in Bone Tissue Engineering

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