Resveratrol and Celastrol Loaded Collagen Dental Implants Regulate Periodontal Ligament Fibroblast Growth and Osteoclastogenesis of Bone Marrow Macrophages

Wang, Ruijie; Bao, Bin; Bao, Chunling; Wang, Shujun; Rahman, Saeed Ur; Hou, Chunyu; Elango, Jeevithan; Wu, Wenhui

doi:10.1002/cbdv.202000295

Cited by 10 publications

(7 citation statements)

References 50 publications

(56 reference statements)

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“…Our results demonstrated that celastrol significantly inhibited mature osteoclast function via the bone resorption pit assay. In line with our results, Wang's research also found that celastrol had an inhibitory effect on osteoclast differentiation (Wang et al, 2020). Additionally, we also observed reduced F-actin formation in mature osteoclasts that was associated with impaired bone resorption activity following celastrol treatment.…”

Section: Discussionsupporting

confidence: 92%

Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

Chen

et al. 2021

Front. Pharmacol.

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Excessive bone resorption by osteoclasts contributes significantly to osteoclast-related diseases such as periprosthetic osteolysis and osteoporosis. Osteolysis in a titanium particle-induced calvarial model and bone loss in an ovariectomized mice model occurred similarly to those in humans; thus, these models can be used to evaluate potential therapies for aseptic prosthetic loosening and osteoporosis. Celastrol, which is extracted from the seeds of the genus Tripterygium, has been thoroughly investigated for its anti-inflammatory and anti-cancer pharmacological effects. However, the mechanisms involving bone metabolism by which celastrol inhibits osteoclastogenesis are not yet fully understood. We demonstrated that celastrol inhibited the receptor activator of nuclear factor κB ligand-induced osteoclastogenesis and the bone resorptive function of osteoclasts in vitro by inhibiting the activation of transforming growth factor β-activated kinase 1-mediated NF-κB and mitogen-activated protein kinase signaling pathways and downregulating osteoclastogenesis marker-related genes. Furthermore, celastrol was also shown to be beneficial in both the titanium particle-induced osteolysis calvarial and the murine ovariectomy-induced bone loss. Collectively, our results suggested that celastrol is promising for the prevention of aseptic prosthetic loosening and osteoporosis in the treatment of osteolytic diseases induced by disrupted osteoclast formation and function.

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Section: Discussionsupporting

confidence: 92%

Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

Chen

et al. 2021

Front. Pharmacol.

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“…Broadly, these design features emphasize the precise configurations for the soluble (biomolecules) and insoluble (material topology) cues within these biomaterial systems for functional tissues and organ systems. 52 – 54 We recently demonstrated the ability of photoactivated latent TGF-β1 directs differentiation of dental stem cells to generate osteodentin. 23 The significance of regenerative dentistry aims to retain the structure and strength of the tooth while preserving pulp vitality.…”

Section: Discussionmentioning

confidence: 99%

Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues

et al. 2022

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The major difference between tissue healing and regeneration is the extent of instructional cues available to precisely direct the biological response. A classic example is reparative or osteodentin that is seen in response to physicochemical injury to the pulp-dentin complex. Dentin regeneration can direct the differentiation of dental stem cells using concerted actions of both soluble (biomolecules, agonists, and antagonists) and insoluble (matrix topology) cues. The major purpose of this study was to examine the synergistic combination of two discrete biomaterial approaches by utilizing nanofiber scaffolds in discrete configurations (aligned or random) with incorporated polymeric microspheres capable of controlled release of growth factors. Further, to ensure appropriate disinfection for clinical use, Radio-Frequency Glow Discharge (RFGD) treatments were utilized, followed by seeding with a mesenchymal stem cell (MSC) line. SEM analysis revealed electrospinning generated controlled architectural features that significantly improved MSC adhesion and proliferation on the aligned nanofiber scaffolds compared to randomly oriented scaffolds. These responses were further enhanced by RFGD pre-treatments. These enhanced cell adhesion and proliferative responses could be attributed to matrix-induced Wnt signaling that was abrogated by pre-treatments with anti-Wnt3a neutralizing antibodies. Next, we incorporated controlled-release microspheres within these electrospun scaffolds with either TGF-β1 or BMP4. We observed that these scaffolds could selectively induce dentinogenic or osteogenic markers (DSPP, Runx2, and BSP) and mineralization. This work demonstrates the utility of a novel, modular combinatorial scaffold system capable of lineage-restricted differentiation into bone or dentin. Future validation of this scaffold system in vivo as a pulp capping agent represents an innovative dentin regenerative approach capable of preserving tooth pulp vitality.

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“…(CEL), and loaded into a collagen film to enhance the effectiveness of coated dental implants by Wang et al [55]. Using SEM and histochemistry, it was determined that the RES-loaded collagen films stimulated the most proliferation of the human periodontal ligamental fibroblasts (HPLFs), whilst the CEL-loaded films, demonstrated the lowest bone marrow macrophage-mediated osteogenesis.…”

Section: Osteoblastic Markermentioning

confidence: 99%

“…Using SEM and histochemistry, it was determined that the RES-loaded collagen films stimulated the most proliferation of the human periodontal ligamental fibroblasts (HPLFs), whilst the CEL-loaded films, demonstrated the lowest bone marrow macrophage-mediated osteogenesis. Hence, it was suggested that using both RES and CEL in the collagen film was a promising approach to the development of an efficacious dental regenerative agent [55].…”

Section: Osteoblastic Markermentioning

confidence: 99%

Trans-Resveratrol: From Phytonutrient Supplement, to Novel Nanotherapeutic Agent

Harney¹

2023

Periodontology - New Insights

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Trans-resveratrol (3,5,4′-trihydroxy-trans-stilbene) (RES) is a plant polyphenol that has been well documented for its anti-oxidant, antimicrobial, anti-inflammatory, and anti-aging properties. Moreover, compelling evidence presented in the abundance of pre-clinical studies using ligature-induced periodontitis models has positioned RES as a theoretically viable candidate for the reduction of the chronic inflammation, oxidative stress, and tissue destruction seen in periodontitis (PD). However, the instability of RES under physiological conditions, as well as its rapid hepatic clearance, has presented as a challenge to its ubiquitous application as an oral therapeutic in clinical practice. Fortunately, with the application of nanotechnology, the pharmacological profile of RES repositions the phytochemical from an herb-based supplement, useful as an adjunct therapy, to a stable and potent nanomedicine, demonstrating efficacy for the prevention and treatment of PD and its associated systemic diseases. This chapter explores the details of the potential for nano-RES as a viable therapeutic for PD.

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Resveratrol and Celastrol Loaded Collagen Dental Implants Regulate Periodontal Ligament Fibroblast Growth and Osteoclastogenesis of Bone Marrow Macrophages

Cited by 10 publications

References 50 publications

Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

Celastrol Attenuates RANKL-Induced Osteoclastogenesis in vitro and Reduces Titanium Particle-Induced Osteolysis and Ovariectomy-Induced Bone Loss in vivo

Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues

Trans-Resveratrol: From Phytonutrient Supplement, to Novel Nanotherapeutic Agent

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