miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress

Hayashi, Chikara; Fukuda, Takao; Kawakami, Kentaro; Toyoda, Masaaki; Nakao, Yoshio; Watanabe, Yukari; Shinjo, Takanori; Sano, Tomomi; Iwashita, Misaki; Yotsumoto, Karen; Shida, Miyu; Taketomi, Takaharu; Sanui, Terukazu; Uchiumi, Takeshi; Kanematsu, Takashi; Nishimura, Fusanori

doi:10.3389/fcell.2022.1061216

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…found similar conclusions where PDLSC‐Exos alleviated an inflammatory microenvironment through the Th17/Treg/miR‐155‐5p/SIRT1 regulatory network, improving periodontitis. Two basic research studies also found that exosomes derived from separate sources were able to significantly decrease immune cell‐driven osteoclastogenesis and prevent bone loss 70,74 . Interestingly, Jarmalavičiūtė et al 64 .…”

Section: Resultsmentioning

confidence: 99%

“…A study by Zheng et al69 found similar conclusions where PDLSC-Exos alleviated an inflammatory microenvironment through the Th17/Treg/miR-155-5p/SIRT1 regulatory network, improving periodontitis. Two basic research studies also found that exosomes derived from separate sources were able to significantly decrease immune cell-driven osteoclastogenesis and prevent bone loss 70,74. Interestingly, Jarmalavičiūtė et al64 found that exosomes specifically (but not microvesicles) derived from SHEDs improved dopaminergic neurons by approximately 80%, suggesting that exosomes derived from SHEDs should be considered a new potential therapeutic tool in the treatment of Parkinson's disease.…”

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confidence: 99%

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Understanding exosomes: Part 3—therapeutic + diagnostic potential in dentistry

Miron,

Estrin,

Sculean

et al. 2024

Periodontology 2000

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Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri‐implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing “remarkable” potential, serving as a valuable tool for clinicians with significant advantages.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Understanding exosomes: Part 3—therapeutic + diagnostic potential in dentistry

Miron,

Estrin,

Sculean

et al. 2024

Periodontology 2000

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“…miR-487b-3p improves chemoresistance or metastasis in osteosarcoma but impairs osteoblastgenesis, and promotes tumorigenesis in colon cancer, prostate cancer and glioma (50)(51)(52)(53)(54). miR-1260b promotes tumorigenesis in breast cancer and lung adenocarcinoma and also inhibits bone loss (55)(56)(57). miR-4758-3p promotes tumorigenesis in glial tumor, gastric cancer and endometrial tumors (58-60), but its association with osteosarcoma is unknown.…”

Section: Discussionmentioning

confidence: 99%

A validation study for the utility of serum microRNA as a diagnostic and prognostic marker in patients with osteosarcoma

et al. 2023

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In our previous study, osteosarcoma advanced locally, and metastasis was promoted through the secretion of large number of small extracellular vesicles, followed by suppressing osteoclastogenesis via the upregulation of microRNA (miR)-146a-5p. An additional 12 miRNAs in small extracellular vesicles were also detected ≥6x as frequently in high-grade malignancy with the capacity to metastasize as in those with a low metastatic potential. However, the utility of these 13 miRNAs for determining the prognosis or diagnosis of osteosarcoma has not been validated in the clinical setting. In the present study, the utility of these miRNAs as prognostic and diagnostic markers was therefore assessed. In total, 30 patients with osteosarcoma were retrospectively reviewed, and the survival rate was compared according to the serum miRNA levels in 27 patients treated with chemotherapy and surgery. In addition, to confirm diagnostic competency for osteosarcoma, the serum miRNA levels were compared with those in patients with other bone tumors (n=112) and healthy controls (n=275). The patients with osteosarcoma with high serum levels of several miRNAs (miR-146a-5p, miR-1260a, miR-487b-3p, miR-1260b and miR-4758-3p) exhibited an improved survival rate compared with those with low levels. In particular, patients with high serum levels of miR-1260a exhibited a significantly improved overall survival rate, metastasis-free survival rate and disease-free survival rate compared with those with low levels. Thus, serum miR-1260a may potentially be a prognostic marker for patients with osteosarcoma. Moreover, patients with osteosarcoma had higher serum miR-1261 levels than those with benign or intermediate-grade bone tumors and thus may be a potential therapeutic target, in addition to being useful for differentiating whether or not a bone tumor is high-grade. A larger investigation is required to clarify the actual utility of these miRNAs in the clinical setting.

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“…C57BL/6NCrSlc mice (female, 8-week-old) were purchased from Japan SLC (Hamamatsu, Japan) and used following the guidelines of an institutionally approved animal research protocol (protocol #A21-131-2; Kyushu University). After one week of quarantine and acclimation, ligature-induced periodontal mouse model was established as previously described [ 17 ]. Briefly, the mice were randomly classified into the following four groups with different treatments ( n = 6): (1) placebo (PBS), (2) DP-1-derived MVs, (3) luteolin-treated DP-1-derived MVs, and (4) LPS from E. coli or P. gingivalis .…”

Section: Methodsmentioning

confidence: 99%

Luteolin Is a Potential Immunomodulating Natural Compound against Pulpal Inflammation

Kawakami,

Fukuda,

Toyoda

et al. 2024

BioMed Research International

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Aim. The present study evaluated the therapeutic effects of luteolin in alleviating pulpitis of dental pulp- (DP-) derived microvesicles (MVs) via the inhibition of protein kinase R- (PKR-) mediated inflammation. Methodology. Proteomic analysis of immortalized human dental pulp (DP-1) cell-derived MVs was performed to identify PKR-associated molecules. The effect of luteolin on PKR phosphorylation in DP-1 cells and the expression of tumor necrosis factor-α (TNF-α) in THP-1 macrophage-like cells were validated. The effect of luteolin on cell proliferation was compared with that of chemical PKR inhibitors (C16 and 2-AP) and the unique commercially available sedative guaiacol-parachlorophenol. In the dog experimental pulpitis model, the pulps were treated with (1) saline, (2) guaiacol-parachlorophenol, and (3) luteolin. Sixteen teeth from four dogs were extracted, and the pulp tissues were analyzed using hematoxylin and eosin staining. Immunohistochemical staining was performed to analyze the expression of phosphorylated PKR (pPKR), myeloperoxidase (MPO), and CD68. Experimental endodontic-periodontal complex lesions were established in mouse molar through a silk ligature and simultaneous MV injection. MVs were prepared from DP-1 cells with or without pretreatment with 2-AP or luteolin. A three-dimensional microcomputed tomography analysis was performed on day 7 (n=6). Periodontal bone resorption volumes were calculated for each group (nonligated–ligated), and the ratio of bone volume to tissue volume was measured. Results. Proteomic analysis identified an endogenous PKR activator, and a protein activator of interferon-induced PKR, also known as PACT, was included in MVs. Luteolin inhibited the expressions of pPKR in DP-1 cells and TNF-α in THP-1 cells with the lowest suppression of cell proliferation. In the dog model of experimental pulpitis, luteolin treatment suppressed the expression of pPKR-, MPO-, and CD68-positive cells in pulp tissues, whereas guaiacol-parachlorophenol treatment caused coagulative necrosis and disruption. In a mouse model of endodontic-periodontal complex lesions, luteolin treatment significantly decreased MV-induced alveolar bone resorption. Conclusion. Luteolin is an effective and safe compound that inhibits PKR activation in DP-derived MVs, enabling pulp preservation.

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miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress

Cited by 9 publications

References 42 publications

Understanding exosomes: Part 3—therapeutic + diagnostic potential in dentistry

Understanding exosomes: Part 3—therapeutic + diagnostic potential in dentistry

A validation study for the utility of serum microRNA as a diagnostic and prognostic marker in patients with osteosarcoma

Luteolin Is a Potential Immunomodulating Natural Compound against Pulpal Inflammation

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