A Three-in-One Strategy: Injectable Biomimetic Porous Hydrogels for Accelerating Bone Regeneration via Shape-Adaptable Scaffolds, Controllable Magnesium Ion Release, and Enhanced Osteogenic Differentiation

Due to their specific mesoporous structure and large surface area, mesoporous bioactive glasses (MBGs) possess both drug-delivery ability and effective ionic release to promote bone regeneration by stimulating osteogenesis and angiogenesis. Macrophages secrete mediators that can affect both processes, depending on their phenotype. In this work, the action of ion release from MBG-75S, with a molar composition of 75SiO2-20CaO-5P2O5, on osteogenesis and angiogenesis and the modulatory role of macrophages have been assessed in vitro with MC3T3-E1 pre-osteoblasts and endothelial progenitor cells (EPCs) in monoculture and in coculture with RAW 264.7 macrophages. Ca2+, phosphorous, and silicon ions released from MBG-75S were measured in the culture medium during both differentiation processes. Alkaline phosphatase activity and matrix mineralization were quantified as the key markers of osteogenic differentiation in MC3T3-E1 cells. The expression of CD31, CD34, VEGFR2, eNOS, and vWF was evaluated to characterize the EPC differentiation into mature endothelial cells. Other cellular parameters analyzed included the cell size and complexity, intracellular calcium, and intracellular content of the reactive oxygen species. The results obtained indicate that the ions released by MBG-75S promote osteogenesis and angiogenesis in vitro, evidencing a macrophage inhibitory role in these processes and demonstrating the high potential of MBG-75S for the preparation of implants for bone regeneration.

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Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02149-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zimo Zhou ◽

Mohammad Showkat Hossain ◽

Da Liu

Keyword(s):

Bone Regeneration ◽

Osteogenic Differentiation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Osteoblast Differentiation ◽

Osteoclast Differentiation ◽

Complex Processes ◽

Osteogenic Induction ◽

Novel Target

AbstractOsteogenic differentiation and bone regeneration are complex processes involving multiple genes and multiple steps. In this review, we summarize the effects of the long noncoding RNA (lncRNA) H19 on osteogenic differentiation.Osteogenic differentiation includes matrix secretion and calcium mineralization as hallmarks of osteoblast differentiation and the absorption of calcium and phosphorus as hallmarks of osteoclast differentiation. Mesenchymal stem cells (MSCs) form osteoprogenitor cells, pre-osteoblasts, mature osteoblasts, and osteocytes through induction and differentiation. lncRNAs regulate the expression of coding genes and play essential roles in osteogenic differentiation and bone regeneration. The lncRNA H19 is known to have vital roles in osteogenic induction.This review highlights the role of H19 as a novel target for osteogenic differentiation and the promotion of bone regeneration.

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Osteon-mimetic 3D nanofibrous scaffold enhancing stem cell proliferation and osteogenic differentiation for bone regeneration

Biomaterials Science ◽

10.1039/d1bm01489g ◽

2022 ◽

Author(s):

Ting Song ◽

Jianhua Zhou ◽

Ming Shi ◽

Liuyang Xuan ◽

Huamin Jiang ◽

...

Keyword(s):

Tissue Engineering ◽

Cell Proliferation ◽

Stem Cell ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Nanofibrous Scaffold ◽

Hierarchical Microstructure ◽

Stem Cell Proliferation

Scaffold microstructure is important for bone tissue engineering. Failure to synergistically imitate the hierarchical microstructure of bone component, such as osteon with concentric multilayers assembled by nanofibers, hindered the performance...

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Engineered Fe(OH)3 nanoparticle-coated and rhBMP-2-releasing PLGA microsphere scaffolds for promoting bone regeneration by facilitating cell homing and osteogenic differentiation

Journal of Materials Chemistry B ◽

10.1039/c8tb00569a ◽

2018 ◽

Vol 6 (18) ◽

pp. 2831-2842 ◽

Cited By ~ 5

Author(s):

Fen Zhang ◽

Qingtao Li ◽

Zefeng Lin ◽

Limin Ma ◽

Sheng Xu ◽

...

Keyword(s):

Bone Regeneration ◽

Osteogenic Differentiation ◽

Plga Microsphere ◽

Cell Homing

Iron facilitates cell homing and enhances the capacity of rhBMP-2.

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PPARβ/δ accelerates bone regeneration in diabetic mellitus by enhancing AMPK/mTOR pathway-mediated autophagy

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02628-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Miao Chen ◽

Dian Jing ◽

Rui Ye ◽

Jianru Yi ◽

Zhihe Zhao

Keyword(s):

Bone Regeneration ◽

Osteogenic Differentiation ◽

Bone Healing ◽

High Glucose ◽

Diabetic Rats ◽

Diabetic Patients ◽

Regulatory Effect ◽

Compound C ◽

High Glucose Condition ◽

Glucose Condition

Abstract Background Diabetic patients are more vulnerable to skeletal complications. Peroxisome proliferators-activated receptor (PPAR) β/δ has a positive regulatory effect on bone turnover under physiologic glucose concentration; however, the regulatory effect in diabetes mellitus has not been investigated yet. Herein, we explored the effects of PPARβ/δ agonist on the regeneration of diabetic bone defects and the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) under a pathological high-glucose condition. Methods We detected the effect of PPARβ/δ agonist on osteogenic differentiation of rBMSCs in vitro and investigated the bone healing process in diabetic rats after PPARβ/δ agonist treatment in vivo. RNA sequencing was performed to detect the differentially expressed genes and enriched pathways. Western blot was performed to detect the autophagy-related protein level. Laser confocal microscope (LSCM) and transmission electron microscope (TEM) were used to observe the formation of autophagosomes. Results Our results demonstrated that the activation of PPARβ/δ can improve the osteogenic differentiation of rBMSCs in high-glucose condition and promote the bone regeneration of calvarial defects in diabetic rats, while the inhibition of PPARβ/δ alleviated the osteogenic differentiation of rBMSCs. Mechanistically, the activation of PPARβ/δ up-regulates AMPK phosphorylation, yielding mTOR suppression and resulting in enhanced autophagy activity, which further promotes the osteogenic differentiation of rBMSCs in high-glucose condition. The addition of AMPK inhibitor Compound C or autophagy inhibitor 3-MA inhibited the osteogenesis of rBMSCs in high-glucose condition, suggesting that PPARβ/δ agonist promotes osteogenic differentiation of rBMSCs through AMPK/mTOR-regulated autophagy. Conclusion In conclusion, our study demonstrates the potential role of PPARβ/δ as a molecular target for the treatment of impaired bone quality and delayed bone healing in diabetic patients for the first time.

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The secreted protein DEL-1 activates a β3 integrin–FAK–ERK1/2–RUNX2 pathway and promotes osteogenic differentiation and bone regeneration

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.013024 ◽

2020 ◽

Vol 295 (21) ◽

pp. 7261-7273 ◽

Cited By ~ 4

Author(s):

Da-Yo Yuh ◽

Tomoki Maekawa ◽

Xiaofei Li ◽

Tetsuhiro Kajikawa ◽

Khalil Bdeir ◽

...

Keyword(s):

Transcription Factor ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Secreted Protein ◽

Dependent Manner ◽

Point Mutant ◽

Rgd Motif ◽

Β3 Integrin ◽

Defective Bone

The integrin-binding secreted protein developmental endothelial locus-1 (DEL-1) is involved in the regulation of both the initiation and resolution of inflammation in different diseases, including periodontitis, an oral disorder characterized by inflammatory bone loss. Here, using a mouse model of bone regeneration and in vitro cell-based mechanistic studies, we investigated whether and how DEL-1 can promote alveolar bone regeneration during resolution of experimental periodontitis. Compared with WT mice, mice lacking DEL-1 or expressing a DEL-1 variant with an Asp-to-Glu substitution in the RGD motif (“RGE point mutant”), which does not interact with RGD-dependent integrins, exhibited defective bone regeneration. Local administration of DEL-1 or of its N-terminal segment containing the integrin-binding RGD motif, but not of the RGE point mutant, reversed the defective bone regeneration in the DEL-1–deficient mice. Moreover, DEL-1 (but not the RGE point mutant) promoted osteogenic differentiation of MC3T3-E1 osteoprogenitor cells or of primary calvarial osteoblastic cells in a β3 integrin–dependent manner. The ability of DEL-1 to promote in vitro osteogenesis, indicated by induction of osteogenic genes such as the master transcription factor Runt-related transcription factor-2 (Runx2) and by mineralized nodule formation, depended on its capacity to induce the phosphorylation of focal adhesion kinase (FAK) and of extracellular signal-regulated kinase 1/2 (ERK1/2). We conclude that DEL-1 can activate a β3 integrin–FAK–ERK1/2–RUNX2 pathway in osteoprogenitors and promote new bone formation in mice. These findings suggest that DEL-1 may be therapeutically exploited to restore bone lost due to periodontitis and perhaps other osteolytic conditions.

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