BDNF/HMW‐HA complex as an adjunct to nonsurgical periodontal treatment of ligature‐induced periodontitis in dogs

Sasaki, Susumu; Takeda, Katsuhiro; Manabu, Takewaki; Ouhara, Kazuhisa; Kajiya, Mikihito; Mizuno, Noriyoshi; Fujita, Tsuyoshi; Kurihara, Hidemi

doi:10.1002/jper.18-0070

Cited by 14 publications

(17 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we demonstrated that cytokine treatment inhibited miR‐628‐5p expression, confirming that cytokines positively regulate MSC osteogenesis via miR‐628‐5p downregulation, whereas miR‐628‐5p overexpression had an opposite effect, resulting in the suppression of MSC osteogenesis. The majority of tested cytokines have been reported to induce periodontal regeneration, including cementogenesis/osteogenesis 6,12,22,29 . These findings suggest that the roles of cytokines in these developmental pathways are more complex than demonstrated in our experiments.…”

Section: Discussionsupporting

confidence: 48%

See 1 more Smart Citation

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

Iwata

Mizuno

Nagahara

et al. 2021

Journal of Periodontology

Self Cite

View full text Add to dashboard Cite

Background Cytokines play key roles in stimulating periodontal regeneration; however, their exact mechanisms of action remain unclear. Mesenchymal stem cells (MSCs) are multipotent cells that have self‐renewal abilities and can differentiate into periodontal tissues such as bone, cementum, and periodontal ligaments following transplantation, like periodontal progenitor cells. Here, we used MSCs to identify the regulatory genes induced by periodontal regenerative cytokines. Methods Human MSCs (hMSCs) were cultured under conditions of periodontal regenerative cytokine stimulation or silencing of undifferentiated hMSC transcription factors. To characterize the changes associated with periodontal regenerative cytokine‐regulated microRNAs (miRNAs), miRNA, and mRNA expression was evaluated using miRNA arrays and quantitative real‐time polymerase chain reaction, respectively. One of the identified miRNAs, miR‐628‐5p, was then overexpressed or suppressed in hMSCs during osteogenesis; the effect of these changes on osteogenesis was investigated. Results Cytokine‐stimulated MSCs showed characteristic miRNA profiles and mRNA levels of undifferentiated hMSC transcription factors ETV1, SOX11, and GATA6. Next, we silenced these transcription factors in MSCs and examined the miRNA profiles. The levels of miR‐628‐5p were decreased upon all cytokine treatments and were increased upon silencing of ETV1, SOX11, and GATA6. Overexpression of miR‐628‐5p suppressed osteogenesis; however, its inhibition enhanced OPN, ALP, OC, BMP2, and RUNX2 mRNA levels, and bone matrix mineralization, but not OSX mRNA or ALP activity. Conclusions miR‐628‐5p negatively regulates MSC stemness during periodontal regeneration. Periodontal regenerative cytokines act as miR‐628‐5p suppressors to support periodontal regeneration. Thus, selection of effective cytokines for different MSCs, based on miRNA profiling, is important for advancing regenerative therapies.

show abstract

Section: Discussionsupporting

confidence: 48%

“…BDNF is another growth factor also associated with periodontal regeneration 29,40 and the regulation of cell functions 5,29 . In our study, BDNF only upregulated ETV1 , even though it affected the expression of most examined miRNAs.…”

Section: Discussionmentioning

confidence: 43%

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

Iwata

Mizuno

Nagahara

et al. 2021

Journal of Periodontology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Researchers have found that PHF8 regulates the development of craniomaxillofacial bone by controlling the methylation of histone sites H4K20 and H3K9. 10 In addition, recent studies have shown that PHF8 is involved in the regulation of brain-derived neurotrophic factor (BDNF) expression, 11 and BDNF has been confirmed to participate in periodontal tissue regeneration, 12,13 which further suggests that PHF8 may participate in the periodontal tissue regeneration process. Bone regeneration is an important aspect of periodontal tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Liu

et al. 2020

Journal of Periodontology

View full text Add to dashboard Cite

Background: Histone methylation is considered to play an important role in the occurrence and development of periodontitis. Plant homeodomain finger protein 8 (PHF8), a histone demethylase, has been shown to regulate inflammation and osteogenic differentiation of bone marrow stromal cells (BMSCs). This study aimed to detect the functions of PHF8 and TLR4 in osteogenic differentiation in an inflammatory environment induced by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) Methods: A periodontitis mouse model was established, and the mice were treated with TAK-242. Immunohistochemical staining was used to detect the expression of PHF8 in periodontal tissue. Periodontal ligament cells (PDLCs) were treated with mineralization induction medium supplemented with Pg-LPS and/or TAK-242, and a Cell Counting Kit-8 (CCK-8) assay was used to detect the proliferation of PDLCs. Real-time PCR and western blotting were used to detect the mRNA and protein expression levels, respectively, of PHF8, toll-like receptor 4 (TLR4) and the other osteogenic markers alkaline phosphatase (ALP), osteocalcin (OCN), Special AT-rich sequence-binding protein 2 (Satb2) and Runt-related transcription factor 2 (Runx2) Results: Periodontitis reduced PHF8 expression in periodontal tissue, and TAK-242 partially reversed this downregulation. An in vitro experiment revealed that the mRNA and protein expression levels of PHF8 were significantly upregulated during the osteogenic differentiation of PDLCs. Alizarin red staining showed that the mineralized nodules of PDLCs in osteogenic induction group were more than those in control group. Real-time PCR and western blot results indicated that Pg-LPS inhibited PHF8 expression and upregulated TLR4 expression in PDLCs.TAK-242 inhibited TLR4 and partially reversed the inhibition of PHF8 expression and osteogenic differentiation induced by Pg-LPS in PDLCs Conclusion: PHF8 and TLR4 play important roles in periodontitis. Pg-LPS inhibits the expression of PHF8 via upregulation of TLR4 and might further inhibit the osteogenic differentiation of PDLCs. However, the specific mechanisms involved remain to be explored.

show abstract

“…Therefore, cementum and periodontal ligament regeneration is the most important concern for structural and functional regeneration of periodontal tissue in periodontal regenerative therapy. Previous research in periodontal regenerative therapy has focused on two primary strategies: cytokine therapy, which can activate tissue regenerative ability possessed by local periodontal cells, [1][2][3][4] and cell transplantation with mesenchymal stem cells (MSCs) or other cells for large and complex periodontal tissue destruction. [5][6][7][8] MSC transplantation can induce new cementum on the root dentin surface, and MSCs can differentiate into cementoblasts.…”

Section: Introductionmentioning

confidence: 99%

Identification of regulatory mRNA and microRNA for differentiation into cementoblasts and periodontal ligament cells

Iwata

Mizuno

Nagahara

et al. 2020

J of Periodontal Research

Self Cite

View full text Add to dashboard Cite

Objective Periodontitis causes periodontal tissue destruction and results in physiological tooth dysfunction. Therefore, periodontal regeneration is ideal therapy for periodontitis. Mesenchymal stem cells (MSCs) are useful for periodontal regenerative therapy as they can differentiate into periodontal cells; however, the underlying regulatory mechanism is unclear. In this study, we attempted to identify regulatory genes involved in periodontal cell differentiation and clarify the differentiation mechanism for effective periodontal regenerative therapy. Background The cementum and periodontal ligament play important roles in physiological tooth function. Therefore, cementum and periodontal ligament regeneration are critical for periodontal regenerative therapy. Mesenchymal stem cell transplantation can be a common periodontal regenerative therapy because these cells have multipotency and self‐renewal ability, which induces new cementum or periodontal ligament formation. Moreover, MSCs can differentiate into cementoblasts. Cementoblast‐ or periodontal ligament cell–specific proteins have been reported; however, it is unclear how these proteins are regulated. MicroRNA (miRNA) can also act as a key regulator of MSC function. Therefore, in this study, we identified regulatory genes involved in cementoblast or periodontal cell differentiation and commitment. Methods Human MSCs (hMSCs), cementoblasts (HCEM), and periodontal ligament cells (HPL cells) were cultured, and mRNA or miRNA expression was evaluated. Additionally, cementoblast‐specific genes were overexpressed or suppressed in hMSCs and their expression levels were investigated. Results HCEM and HPL cells expressed characteristic genes, of which we focused on ets variant 1 (ETV1), miR‐628‐5p, and miR‐383 because ETV1 is a differentiation‐related transcription factor, miR‐628‐5p was the second‐highest expressed gene in HCEM and lowest expressed gene in HPL cells, and miR‐383 was the highest expressed gene in HCEM. miR‐628‐5p and miR‐383 overexpression in hMSCs regulated ETV1 mRNA expression, and miR‐383 overexpression downregulated miR‐628‐5p expression. Moreover, miR‐383 suppression decreased miR‐383 expression and enhanced ETV1 mRNA expression, but miR‐383 suppression also decreased miR‐628‐5p. Furthermore, silencing of ETV1 expression in hMSCs regulated miR‐628‐5p and miR‐383 expression. Concerning periodontal cell commitment, miR‐628‐5p, miR‐383, and ETV1 regulated the expression of HCEM‐ or HPL cell–related genes by adjusting the expression of these miRNAs. Conclusion HCEM and HPL cells show characteristic mRNA and miRNA profiles. In particular, these cells have specific miR‐383, miR‐628‐5p, and ETV1 expression patterns, and these genes interact with each other. Therefore, miR‐383, miR‐628‐5p, and ETV1 are key genes involved in cementogenesis or HPL cell differentiation.

show abstract

BDNF/HMW‐HA complex as an adjunct to nonsurgical periodontal treatment of ligature‐induced periodontitis in dogs

Abstract: BDNF/HMW-HA complex as an adjunct to nonsurgical periodontal treatment has the potential to reduce excess inflammation. Further investigation will be needed to clarify periodontal tissue regenerative effects of BDNF/HMW-HA complex in a nonsurgical setting.

Cited by 14 publications

References 43 publications

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

Cytokines regulate stemness of mesenchymal stem cells via miR‐628‐5p during periodontal regeneration

The role of PHF8 and TLR4 in osteogenic differentiation of periodontal ligament cells in inflammatory environment

Identification of regulatory mRNA and microRNA for differentiation into cementoblasts and periodontal ligament cells

Contact Info

Product

Resources

About