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Elmanfi S, Onyedibe KI, Aryal UK, Könönen E, Sintim HO, Gürsoy UK. Activation of cellular responses by cyclic dinucleotides and porphyromonas gingivalis lipopolysaccharide: a proteomic study on gingival fibroblasts. J Oral Microbiol 2024; 17:2431453. [PMID: 39669221 PMCID: PMC11632945 DOI: 10.1080/20002297.2024.2431453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 09/02/2024] [Accepted: 09/17/2024] [Indexed: 12/14/2024] Open
Abstract
Background Bacterial cyclic dinucleotides (CDNs), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) upregulate interferon signaling proteins of human gingival fibroblasts (HGFs). However, the simultaneous effect of bacterial CDNs and lipopolysaccharides (LPS) on the HGF proteome is unknown. Aim The aim was to apply an unbiased proteomics approach to evaluate how simultaneous exposure to CDNs and Porphyromonas gingivalis (Pg) LPS affect the global proteome of HGFs. Methods The proteomic responses of HGFs were examined under three different treatment conditions (c-di-AMP+Pg LPS, c-di-GMP+Pg LPS, and Pg LPS alone) by label-free quantitative mass spectrometry analysis. Results Simultaneous exposure to CDNs and Pg LPS significantly upregulated innate immunity-related and interferon signaling-related proteins, such as ubiquitin-like protein ISG15 (ISG15), deoxynucleoside triphosphate triphosphohydrolase (SAMHD1), interferon regulatory factor 9 (IRF-9), interferon-induced GTP-binding protein Mx (MX)1, and MX2. Interferon signaling pathway was the most significantly regulated canonical pathway in both CDN treatment groups. Conclusion Simultaneous exposure to CDNs and Pg LPS stimulates the periodontal immune response by activating the anti-microbial cellular responses of HGFs with some notable differences from individual exposures.
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Affiliation(s)
- Samira Elmanfi
- Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland
| | - Kenneth I. Onyedibe
- Department of Chemistry, Purdue University, West Lafayette, USA
- Purdue Institute for Inflammation, Immunology and Infectious Disease and Purdue Institute for Drug Discovery, Purdue University, West Lafayette, USA
- Department of Biomedical Sciences, Mercer University School of Medicine, MaconGA, USA
| | - Uma K. Aryal
- Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, USA
- Department of Comparative Pathobiology, Purdue University, West Lafayette, USA
| | - Eija Könönen
- Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland
| | - Herman O. Sintim
- Department of Chemistry, Purdue University, West Lafayette, USA
- Purdue Institute for Inflammation, Immunology and Infectious Disease and Purdue Institute for Drug Discovery, Purdue University, West Lafayette, USA
| | - Ulvi Kahraman Gürsoy
- Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland
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Ijaz MU, Imtiaz S, Hayat MF, Batool M, Al-Ghanim KA, Riaz MN. Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf-2/Keap-1, Inflammatory, Steroidogenic, and Histological Profile. ENVIRONMENTAL TOXICOLOGY 2024; 39:5284-5295. [PMID: 39179512 DOI: 10.1002/tox.24408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/14/2024] [Accepted: 08/10/2024] [Indexed: 08/26/2024]
Abstract
Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ-induced testicular toxicity in rats. Forty-eight male rats (Rattus norvegicus) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap-1 while downregulating the expression of 3-beta hydroxysteroid dehydrogenase (3β-HSD), 17-beta hydroxysteroid dehydrogenase (17β-HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-1beta (IL-1β), and cyclooxygenase-2 (COX-2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate-specific proteases-3 (Caspase-3) and Bcl-2-associated X-protein (Bax) while downregulating the expressions of B-cell lymphoma-2 (Bcl-2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti-inflammatory, and androgenic potential.
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Affiliation(s)
- Muhammad Umar Ijaz
- Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan
| | - Sana Imtiaz
- Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan
| | - Muhammad Faisal Hayat
- Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan
| | - Moazama Batool
- Department of Zoology, Govt. College Women University, Sialkot, Pakistan
| | - Khalid A Al-Ghanim
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
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3
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Falatah AM, Alturki SA, Aldahami AI, Alrashidi NA, Sinnah Y, Aldgeel RM, Alanazi KZ, Alkhaled AS, ALjuaid TS, Alotaibi NH, Altwijri WJ. Exploring the Influence of Genetic Single-Nucleotide Polymorphism (SNPs) on Endodontic Pathologies: A Comprehensive Review. Cureus 2024; 16:e74389. [PMID: 39723289 PMCID: PMC11669393 DOI: 10.7759/cureus.74389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2024] [Indexed: 12/28/2024] Open
Abstract
A considerable portion of the global population is affected by pulpitis and periapical lesions. While the impact of infections caused by various microbes and host effector molecules in pulpal and periapical diseases is widely recognized, disease susceptibility and progression are also influenced by the dynamic interaction between host genetic factors and environmental influences. Apical periodontitis occurs as an inflammatory response to microorganisms present in the root canals of infected teeth. Initially functioning as the body's defense mechanism, this response often progresses to chronic inflammation. Several studies have established associations between genetic polymorphisms and various dental conditions, including temporomandibular joint (TMJ) disorders, dental caries, orthognathic surgeries, open bite malocclusion, periapical periodontitis, pulp stones, pulpitis, periapical abscesses, local anesthesia complications, and endodontic treatment outcomes. Key findings from this review highlight the role of specific single-nucleotide polymorphisms (SNPs) in genes such as matrix metalloproteinase (MMP)1, MMP2, MMP3, interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-alpha (TNF-α), which influence inflammatory pathways and tissue remodeling. For example, SNPs in interleukin genes, such as IL-1β (-511 C/T), have been linked to an increased risk of apical periodontitis, while MMP gene polymorphisms contribute to tissue degradation in periapical lesions. This review underscores the importance of identifying genetic markers that drive disease progression and inflammatory processes in pulpal and periapical pathologies. A better understanding of these mechanisms can inform strategies for disease prevention, personalized treatment approaches, and improved endodontic outcomes.
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Affiliation(s)
| | | | - Abdulatif I Aldahami
- Dentistry, Qassim University, Bachelor Degree of Dental Surgery (BDS), Buraydah, SAU
| | | | | | | | | | - Amira S Alkhaled
- College of Dentistry, King Saud bin Abdulaziz University for Health Sciences, Riyadh, SAU
| | | | | | - Worod J Altwijri
- Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, SAU
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4
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Maccaferri M, Pisciotta A, Carnevale G, Salvarani C, Pignatti E. Human dental pulp stem cells modulate pro-inflammatory macrophages both through cell-to-cell contact and paracrine signaling. Front Immunol 2024; 15:1440974. [PMID: 39450172 PMCID: PMC11499095 DOI: 10.3389/fimmu.2024.1440974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 09/23/2024] [Indexed: 10/26/2024] Open
Abstract
Introduction Macrophages play a key role in most of the inflammatory diseases such as Rheumatoid Arthritis (RA), but the mechanism underlying their pathogenesis is still under study. Among stem cells, human dental pulp stem cells (hDPSCs) have attracted attention due to their easy accessibility and immunomodulatory properties, making them a promising adjuvant therapy. In this study, we aimed to evaluate the capacity of hDPSCs to modulate the phenotypes of primary human macrophages. Additionally, we sought to observe the differences induced on macrophages when cultured directly with hDPSCs or through a cell culture insert, mimicking the paracrine communication pathway. Methods Monocytes, isolated from buffy coats, were differentiated into pro-inflammatory M1 and anti-inflammatory M2 macrophages. Subsequently, they were cultured with hDPSCs either directly or via a cell-culture insert for 48 hours. Finally, they were analyzed for protein, gene expression, cytokines levels and immunofluorescence. Results In our study, we have demonstrated that, hDPSCs, even without priming, can reduce TNFα levels and enhancing IL-10 release in pro-inflammatory macrophages, both through direct contact and paracrine signaling. Furthermore, we found that their effects are more pronounced when in cell-to-cell contact through the decrease of NF-kB and COX-2 expression and of CD80/PD-L1 colocalization. HDPSCs, when in contact with macrophages, showed enhanced expression of NF-kB, COX-2, ICAM-1, PD-L1, FAS-L, TNFα and IFNγ. Conclusion We showed that hDPSCs exert immunomodulatory effects on pro-inflammatory macrophages, with cell-to-cell contact yielding a more pronounced outcome compared to paracrine signaling. Our work highlights the immunomodulatory properties of hDPSCs on activated pro-inflammatory macrophages and the potential therapeutic role in inflamed tissue.
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Affiliation(s)
- Monia Maccaferri
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandra Pisciotta
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Gianluca Carnevale
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Carlo Salvarani
- Rheumatology Unit, Azienda Unità Sanitaria Locale - Istituto di Ricovero e Cura a Carattere Scientifico (USL-IRCCS) di Reggio Emilia, Reggio Emilia, Italy
| | - Elisa Pignatti
- Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
- Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
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5
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Chen Z, Lang G, Xu X, Liang X, Han Y, Han Y. The role of NF-kappaB in the inflammatory processes related to dental caries, pulpitis, apical periodontitis, and periodontitis-a narrative review. PeerJ 2024; 12:e17953. [PMID: 39221277 PMCID: PMC11366231 DOI: 10.7717/peerj.17953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024] Open
Abstract
Tooth-related inflammatory disorders, including caries, pulpitis, apical periodontitis (AP), and periodontitis (PD), are primarily caused by resident oral microorganisms. Although these dental inflammatory conditions are typically not life-threatening, neglecting them can result in significant complications and greatly reduce an individual's quality of life. Nuclear factor κB (NF-κB), a family formed by various combinations of Rel proteins, is extensively involved in inflammatory diseases and even cancer. This study reviews recent data on NF-κB signaling and its role in dental pulp stem cells (DPSCs), dental pulp fibroblasts (DPFs), odontoblasts, human periodontal ligament cells (hPDLCs), and various experimental animal models. The findings indicate that NF-κB signaling is abnormally activated in caries, pulpitis, AP, and PD, leading to changes in related cellular differentiation. Under specific conditions, NF-κB signaling occasionally interacts with other signaling pathways, affecting inflammation, bone metabolism, and tissue regeneration processes. In summary, data collected over recent years confirm the central role of NF-κB in dental inflammatory diseases, potentially providing new insights for drug development targeting NF-κB signaling pathways in the treatment of these conditions. Keywords: NF-κB, dental caries, pulpitis, apical periodontitis, periodontitis.
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Affiliation(s)
- Zhonglan Chen
- Zunyi Medical University, Special Key Laboratory of Oral Diseases Research, Hospital/School of Stomatology, Zunyi, Guizhou, China
| | - Guangping Lang
- Zunyi Medical University, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi, Guizhou, China
| | - Xi Xu
- Zunyi Medical University, Special Key Laboratory of Oral Diseases Research, Hospital/School of Stomatology, Zunyi, Guizhou, China
| | - Xinghua Liang
- Zunyi Medical University, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi, Guizhou, China
| | - Yalin Han
- Zunyi Medical University, Special Key Laboratory of Oral Diseases Research, Hospital/School of Stomatology, Zunyi, Guizhou, China
| | - Yingying Han
- Zunyi Medical University, Special Key Laboratory of Oral Diseases Research, Hospital/School of Stomatology, Zunyi, Guizhou, China
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Hezam K, Fu E, Zhang J, Li Z. Therapeutic trends of priming mesenchymal stem cells: A bibliometric analysis. Biochem Biophys Rep 2024; 38:101708. [PMID: 38623536 PMCID: PMC11016583 DOI: 10.1016/j.bbrep.2024.101708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/22/2024] [Accepted: 04/05/2024] [Indexed: 04/17/2024] Open
Abstract
Mesenchymal stem cells (MSCs) have gained substantial attention in regenerative medicine due to their multilineage differentiation potential and immunomodulatory capabilities. MSCs have demonstrated therapeutic promise in numerous preclinical and clinical studies across a variety of diseases, including neurodegenerative disorders, cardiovascular diseases, and autoimmune conditions. Recently, priming MSCs has emerged as a novel strategy to enhance their therapeutic efficacy by preconditioning them for optimal survival and function in challenging in vivo environments. This study presented a comprehensive bibliometric analysis of research activity in the field of priming mesenchymal stem cells (MSCs) from 2003 to 2023. Utilizing a dataset of 585 documents, we explored research trends, leading authors and countries, productive journals, and frequently used keywords. We also explored priming strategies to augment the therapeutic efficacy of MSCs. Our findings show increasing research productivity with a peak in 2019, identified the United States as the leading contributor, and highlighted WANG JA as the most prolific author. The most published journal was Stem Cell Research & Therapy. Keyword analysis revealed core research areas emerging hotspots, while coword and cited sources visualizations elucidated the conceptual framework and key information sources. Further studies are crucial to advance the translation of primed MSCs from bench to bedside, potentially revolutionizing the landscape of regenerative medicine.
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Affiliation(s)
- Kamal Hezam
- Nankai University School of Medicine, Tianjin, 300071, China
- Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, 300052, China
| | - Enze Fu
- Nankai University School of Medicine, Tianjin, 300071, China
| | - Jun Zhang
- Department of Anesthesiology and Pain Medical Center, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, China
| | - Zongjin Li
- Nankai University School of Medicine, Tianjin, 300071, China
- Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, 300052, China
- National Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, 100853, China
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7
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Nam OH, Kim JH, Kang SW, Chae YK, Jih MK, You HH, Koh JT, Kim Y. Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammation in human dental pulp cells via the PI3K/Akt, NF-κB, and MAPK signalling pathways. Int Endod J 2024; 57:759-768. [PMID: 38436525 DOI: 10.1111/iej.14058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/19/2024] [Accepted: 02/20/2024] [Indexed: 03/05/2024]
Abstract
AIM Among numerous constituents of Panax ginseng, a constituent named Ginsenoside Rb1 (G-Rb1) has been studied to diminish inflammation associated with diseases. This study investigated the anti-inflammatory properties of G-Rb1 on human dental pulp cells (hDPCs) exposed to lipopolysaccharide (LPS) and aimed to determine the underlying molecular mechanisms. METHODOLOGY The KEGG pathway analysis was performed after RNA sequencing in G-Rb1- and LPS-treated hDPCs. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis were used for the assessment of cell adhesion molecules and inflammatory cytokines. Statistical analysis was performed with one-way ANOVA and the Student-Newman-Keuls test. RESULTS G-Rb1 did not exhibit any cytotoxicity within the range of concentrations tested. However, it affected the levels of TNF-α, IL-6 and IL-8, as these showed reduced levels with exposure to LPS. Additionally, less mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were shown. With the presence of G-Rb1, decreased levels of PI3K/Akt, phosphorylated IκBα and p65 were also observed. Furthermore, phosphorylated ERK and JNK by LPS were diminished within 15, 30 and 60 min of G-Rb1 exposure; however, the expression of non-phosphorylated ERK and JNK remained unchanged. CONCLUSIONS G-Rb1 suppressed the LPS-induced increase of cell adhesion molecules and inflammatory cytokines, while also inhibiting PI3K/Akt, phosphorylation of NF-κB transcription factors, ERK and JNK of MAPK signalling in hDPCs.
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Affiliation(s)
- Ok Hyung Nam
- Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, Korea
- Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee Universtiy Medical Center, Seoul, Korea
| | - Jae-Hwan Kim
- Department of Pediatric Dentistry, School of Dentistry, Jeonbuk National University, Jeonju, Korea
| | - Si Won Kang
- Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju, Korea
| | - Yong Kwon Chae
- Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee Universtiy Medical Center, Seoul, Korea
| | - Myeong-Kwan Jih
- Department of Pediatric Dentistry, School of Dentistry, Chosun University, Gwangju, Korea
| | - Hyekyoung Hannah You
- Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju, Korea
| | - Jeong-Tae Koh
- Department of Pharmacology and Dental Therapeutics, Hard-tissue Biointerface Research Center, School of Dentistry, Dental Science Research Institute, Chonnam National University, Gwangju, Korea
| | - Young Kim
- Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju, Korea
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Li P, Jin Q, Zeng K, Niu C, Xie Q, Dong T, Huang Z, Dou X, Feng C. Amino acid-based supramolecular chiral hydrogels promote osteogenesis of human dental pulp stem cells via the MAPK pathway. Mater Today Bio 2024; 25:100971. [PMID: 38347936 PMCID: PMC10859303 DOI: 10.1016/j.mtbio.2024.100971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 01/18/2024] [Accepted: 01/19/2024] [Indexed: 02/15/2024] Open
Abstract
Critical-size defects (CSDs) of the craniofacial bones cause aesthetic and functional complications that seriously impact the quality of life. The transplantation of human dental pulp stem cells (hDPSCs) is a promising strategy for bone tissue engineering. Chirality is commonly observed in natural biomolecules, yet its effect on stem cell differentiation is seldom studied, and little is known about the underlying mechanism. In this study, supramolecular chiral hydrogels were constructed using L/d-phenylalanine (L/D-Phe) derivatives. The results of alkaline phosphatase expression analysis, alizarin red S assay, as well as quantitative real-time polymerase chain reaction and western blot analyses suggest that right-handed D-Phe hydrogel fibers significantly promoted osteogenic differentiation of hDPSCs. A rat model of calvarial defects was created to investigate the regulation of chiral nanofibers on the osteogenic differentiation of hDPSCs in vivo. The results of the animal experiment demonstrated that the D-Phe group exhibited greater and faster bone formation on hDPSCs. The results of RNA sequencing, vinculin immunofluorescence staining, a calcium fluorescence probe assay, and western blot analysis indicated that L-Phe significantly promoted adhesion of hDPSCs, while D-Phe nanofibers enhanced osteogenic differentiation of hDPSCs by facilitating calcium entry into cells and activate the MAPK pathway. These results of chirality-dependent osteogenic differentiation offer a novel therapeutic strategy for the treatment of CSDs by optimising the differentiation of hDPSCs into chiral nanofibers.
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Affiliation(s)
- Peilun Li
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Qiaoqiao Jin
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Kangrui Zeng
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Chenguang Niu
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Qianyang Xie
- Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Ting Dong
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Zhengwei Huang
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
| | - Xiaoqiu Dou
- State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Chuanliang Feng
- State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
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9
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Liu Z, Luo X, Xu R. Interaction between immuno-stem dual lineages in jaw bone formation and injury repair. Front Cell Dev Biol 2024; 12:1359295. [PMID: 38510177 PMCID: PMC10950953 DOI: 10.3389/fcell.2024.1359295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 02/26/2024] [Indexed: 03/22/2024] Open
Abstract
The jawbone, a unique structure in the human body, undergoes faster remodeling than other bones due to the presence of stem cells and its distinct immune microenvironment. Long-term exposure of jawbones to an oral environment rich in microbes results in a complex immune balance, as shown by the higher proportion of activated macrophage in the jaw. Stem cells derived from the jawbone have a higher propensity to differentiate into osteoblasts than those derived from other bones. The unique immune microenvironment of the jaw also promotes osteogenic differentiation of jaw stem cells. Here, we summarize the various types of stem cells and immune cells involved in jawbone reconstruction. We describe the mechanism relationship between immune cells and stem cells, including through the production of inflammatory bodies, secretion of cytokines, activation of signaling pathways, etc. In addition, we also comb out cellular interaction of immune cells and stem cells within the jaw under jaw development, homeostasis maintenance and pathological conditions. This review aims to eclucidate the uniqueness of jawbone in the context of stem cell within immune microenvironment, hopefully advancing clinical regeneration of the jawbone.
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Affiliation(s)
| | | | - Ruoshi Xu
- State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases and Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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10
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Zhou L, Zhao S, Xing X. Effects of different signaling pathways on odontogenic differentiation of dental pulp stem cells: a review. Front Physiol 2023; 14:1272764. [PMID: 37929208 PMCID: PMC10622672 DOI: 10.3389/fphys.2023.1272764] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 10/02/2023] [Indexed: 11/07/2023] Open
Abstract
Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells that can differentiate into odontoblast-like cells and protect the pulp. The differentiation of DPSCs can be influenced by biomaterials or growth factors that activate different signaling pathways in vitro or in vivo. In this review, we summarized six major pathways involved in the odontogenic differentiation of DPSCs, Wnt signaling pathways, Smad signaling pathways, MAPK signaling pathways, NF-kB signaling pathways, PI3K/AKT/mTOR signaling pathways, and Notch signaling pathways. Various factors can influence the odontogenic differentiation of DPSCs through one or more signaling pathways. By understanding the interactions between these signaling pathways, we can expand our knowledge of the mechanisms underlying the regeneration of the pulp-dentin complex.
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Affiliation(s)
| | | | - Xianghui Xing
- Department of Pediatric Dentistry, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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11
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Sturiale V, Bruno F, Brancato D, D’Amico AG, Maugeri G, D’Agata V, Saccone S, Federico C. Cell Cycle Reactivation, at the Start of Neurodegeneration, Induced by Forskolin and Aniline in Differentiated Neuroblastoma Cells. Int J Mol Sci 2023; 24:14373. [PMID: 37762676 PMCID: PMC10531780 DOI: 10.3390/ijms241814373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/19/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
A characteristic hallmark of Alzheimer's disease (AD) is the intracellular accumulation of hyperphosphorylated tau protein, a phenomenon that appears to have associations with oxidative stress, double-stranded DNA breakage, and the de-condensation of heterochromatin. Re-entry into the cell division cycle appears to be involved in the onset of this neurodegenerative process. Indeed, the cell cycle cannot proceed regularly in the differentiated neurons leading to cell death. Here, we induced cell cycle reactivation in neuronal-like cells, obtained by neuroblastoma cells treated with retinoic acid, by exposure to forskolin or aniline. These compounds determine tau hyperphosphorylation or oxidative stress, respectively, resulting in the appearance of features resembling the start of neuronal degeneration typical of AD, such as tau hyperphosphorylation and re-entry into the cell cycle. Indeed, we detected an increased transcriptional level of cyclins and the appearance of a high number of mitotic cells. We also observed a delay in the initiation of the cell cycle when forskolin was co-administered with pituitary adenylate cyclase-activating polypeptide (PACAP). This delay was not observed when PACAP was co-administered with aniline. Our data demonstrate the relevance of tau hyperphosphorylation in initiating an ectopic cell cycle in differentiated neuronal cells, a condition that can lead to neurodegeneration. Moreover, we highlight the utility of neuroblastoma cell lines as an in vitro cellular model to test the possible neuroprotective effects of natural molecules.
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Affiliation(s)
- Valentina Sturiale
- Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy; (V.S.); (F.B.)
| | - Francesca Bruno
- Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy; (V.S.); (F.B.)
| | - Desiree Brancato
- Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy; (V.S.); (F.B.)
| | - Agata Grazia D’Amico
- Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy
| | - Grazia Maugeri
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Velia D’Agata
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Salvatore Saccone
- Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy; (V.S.); (F.B.)
| | - Concetta Federico
- Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy; (V.S.); (F.B.)
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12
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Hezam K, Wang C, Fu E, Zhou M, Liu Y, Wang H, Zhu L, Han Z, Han ZC, Chang Y, Li Z. Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation. Stem Cell Res Ther 2023; 14:48. [PMID: 36949464 PMCID: PMC10032272 DOI: 10.1186/s13287-023-03277-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 03/13/2023] [Indexed: 03/24/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) have demonstrated remarkable therapeutic promise for acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS). MSC secretomes contain various immunoregulatory mediators that modulate both innate and adaptive immune responses. Priming MSCs has been widely considered to boost their therapeutic efficacy for a variety of diseases. Prostaglandin E2 (PGE2) plays a vital role in physiological processes that mediate the regeneration of injured organs. METHODS This work utilized PGE2 to prime MSCs and investigated their therapeutic potential in ALI models. MSCs were obtained from human placental tissue. MSCs were transduced with firefly luciferase (Fluc)/eGFP fusion protein for real-time monitoring of MSC migration. Comprehensive genomic analyses explored the therapeutic effects and molecular mechanisms of PGE2-primed MSCs in LPS-induced ALI models. RESULTS Our results demonstrated that PGE2-MSCs effectively ameliorated lung injury and decreased total cell numbers, neutrophils, macrophages, and protein levels in bronchoalveolar lavage fluid (BALF). Meanwhile, treating ALI mice with PGE2-MSCs dramatically reduced histopathological changes and proinflammatory cytokines while increasing anti-inflammatory cytokines. Furthermore, our findings supported that PGE2 priming improved the therapeutic efficacy of MSCs through M2 macrophage polarization. CONCLUSION PGE2-MSC therapy significantly reduced the severity of LPS-induced ALI in mice by modulating macrophage polarization and cytokine production. This strategy boosts the therapeutic efficacy of MSCs in cell-based ALI therapy.
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Affiliation(s)
- Kamal Hezam
- Nankai University School of Medicine, Tianjin, 300071, China
- Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, 300052, China
- The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, College of Life Sciences, Tianjin, 300071, China
| | - Chen Wang
- Nankai University School of Medicine, Tianjin, 300071, China
- Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, 300052, China
- The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, College of Life Sciences, Tianjin, 300071, China
| | - Enze Fu
- Nankai University School of Medicine, Tianjin, 300071, China
| | - Manqian Zhou
- Department of Radiation Oncology, Tianjin Union Medical Center, Nankai University, Tianjin, 300120, China
| | - Yue Liu
- Nankai University School of Medicine, Tianjin, 300071, China
| | - Hui Wang
- Department of Radiation Oncology, Tianjin Union Medical Center, Nankai University, Tianjin, 300120, China
| | - Lihong Zhu
- Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Zhibo Han
- Jiangxi Engineering Research Center for Stem Cells, Shangrao, 334109, Jiangxi, China
- Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceuticals, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd, Tianjin, 300457, China
- Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., 100176, Beijing, China
| | - Zhong-Chao Han
- Jiangxi Engineering Research Center for Stem Cells, Shangrao, 334109, Jiangxi, China
- Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceuticals, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd, Tianjin, 300457, China
- Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., 100176, Beijing, China
| | - Ying Chang
- Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, 300052, China.
| | - Zongjin Li
- Nankai University School of Medicine, Tianjin, 300071, China.
- Tianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital of Obstetrics and Gynecology, Tianjin, 300052, China.
- The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, College of Life Sciences, Tianjin, 300071, China.
- State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, 100853, China.
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13
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Zhao J, Zhou YH, Zhao YQ, Gao ZR, Ouyang ZY, Ye Q, Liu Q, Chen Y, Tan L, Zhang SH, Feng Y, Hu J, Dusenge MA, Feng YZ, Guo Y. Oral cavity-derived stem cells and preclinical models of jaw-bone defects for bone tissue engineering. Stem Cell Res Ther 2023; 14:39. [PMID: 36927449 PMCID: PMC10022059 DOI: 10.1186/s13287-023-03265-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Jaw-bone defects caused by various diseases lead to aesthetic and functional complications, which can seriously affect the life quality of patients. Current treatments cannot fully meet the needs of reconstruction of jaw-bone defects. Thus, the research and application of bone tissue engineering are a "hot topic." As seed cells for engineering of jaw-bone tissue, oral cavity-derived stem cells have been explored and used widely. Models of jaw-bone defect are excellent tools for the study of bone defect repair in vivo. Different types of bone defect repair require different stem cells and bone defect models. This review aimed to better understand the research status of oral and maxillofacial bone regeneration. MAIN TEXT Data were gathered from PubMed searches and references from relevant studies using the search phrases "bone" AND ("PDLSC" OR "DPSC" OR "SCAP" OR "GMSC" OR "SHED" OR "DFSC" OR "ABMSC" OR "TGPC"); ("jaw" OR "alveolar") AND "bone defect." We screened studies that focus on "bone formation of oral cavity-derived stem cells" and "jaw bone defect models," and reviewed the advantages and disadvantages of oral cavity-derived stem cells and preclinical model of jaw-bone defect models. CONCLUSION The type of cell and animal model should be selected according to the specific research purpose and disease type. This review can provide a foundation for the selection of oral cavity-derived stem cells and defect models in tissue engineering of the jaw bone.
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Affiliation(s)
- Jie Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ying-Hui Zhou
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.,National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Ya-Qing Zhao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Zheng-Rong Gao
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Ze-Yue Ouyang
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Qin Ye
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Qiong Liu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yun Chen
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Li Tan
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Shao-Hui Zhang
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yao Feng
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Jing Hu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Marie Aimee Dusenge
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Yun-Zhi Feng
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
| | - Yue Guo
- Department of Stomatology, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan, China.
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14
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Tayanloo-Beik A, Nikkhah A, Roudsari PP, Aghayan H, Rezaei-Tavirani M, Nasli-Esfahani E, Mafi AR, Nikandish M, Shouroki FF, Arjmand B, Larijani B. Application of Biocompatible Scaffolds in Stem-Cell-Based Dental Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1409:83-110. [PMID: 35999347 DOI: 10.1007/5584_2022_734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Tissue engineering as an important field in regenerative medicine is a promising therapeutic approach to replace or regenerate injured tissues. It consists of three vital steps including the selection of suitable cells, formation of 3d scaffolds, and adding growth factors. Mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) are mentioned as two main sources for this approach that have been used for the treatment of various types of disorders. However, the main focus of literature in the field of dental tissue engineering is on utilizing MSCs. On the other hand, biocompatible scaffolds play a notable role in this regenerative process which is mentioned to be harmless with acceptable osteoinductivity. Their ability in inhibiting inflammatory responses also makes them powerful tools. Indeed, stem cell functions should be supported by biomaterials acting as scaffolds incorporated with biological signals. Naturally derived polymeric scaffolds and synthetically engineered polymeric/ceramic scaffolds are two main types of scaffolds regarding their materials that are defined further in this review. Various strategies of tissue bioengineering can affect the regeneration of dentin-pulp complex, periodontium regeneration, and whole teeth bioengineering. In this regard, in vivo/ex vivo experimental models have been developed recently in order to perform preclinical studies of dental tissue engineering which make it more transferable to be used for clinic uses. This review summarizes dental tissue engineering through its different components. Also, strategies of tissue bioengineering and experimental models are introduced in order to provide a perspective of the potential roles of dental tissue engineering to be used for clinical aims.
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Affiliation(s)
- Akram Tayanloo-Beik
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirabbas Nikkhah
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Peyvand Parhizkar Roudsari
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Aghayan
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Ensieh Nasli-Esfahani
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Rezazadeh Mafi
- Department of Radiation Oncology, Imam Hossein Hospital, Shaheed Beheshti Medical University, Tehran, Iran
| | - Mohsen Nikandish
- AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Fatemeh Fazeli Shouroki
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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15
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Zhou J, Ou MH, Wei XL, Lan BY, Chen WJ, Song SJ, Chen WX. The role of different macrophages-derived conditioned media in dental pulp tissue regeneration. Tissue Cell 2022; 79:101944. [DOI: 10.1016/j.tice.2022.101944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/21/2022] [Accepted: 09/21/2022] [Indexed: 10/14/2022]
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16
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Li J, Wang Z, Wang J, Guo Q, Fu Y, Dai Z, Wang M, Bai Y, Liu X, Cooper PR, Wu J, He W. Amphiregulin regulates odontogenic differentiation of dental pulp stem cells by activation of mitogen-activated protein kinase and the phosphatidylinositol 3-kinase signaling pathways. Stem Cell Res Ther 2022; 13:304. [PMID: 35841013 PMCID: PMC9284861 DOI: 10.1186/s13287-022-02971-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 04/21/2022] [Indexed: 12/14/2022] Open
Abstract
Background Human dental pulp stem cells (hDPSCs) have received widespread attention in the fields of tissue engineering and regenerative medicine. Although amphiregulin (AREG) has been shown to play a vital function in the biological processes of various cell types, its effects on DPSCs remain largely unknown. The aim of this study was to explore the specific role of AREG as a biologically active factor in the regeneration of dental pulp tissue. Methods The growth of hDPSCs, together with their proliferation and apoptosis, in response to AREG was examined by CCK-8 assay and flow cytometry. We explored the effects of AREG on osteo/odontogenic differentiation in vitro and investigated the regeneration and mineralization of hDPSCs in response to AREG in vivo. The effects of AREG gain- and loss-of-function on DPSC differentiation were investigated following transfection using overexpression plasmids and shRNA, respectively. The involvement of the mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the mineralization process and the expression of odontoblastic marker proteins after AREG induction were investigated by using Alizarin Red S staining and Western blotting, respectively. Results AREG (0.01–0.1 µg/mL) treatment of hDPSCs from 1 to 7 days increased hDPSCs growth and affected apoptosis minimally compared with negative controls. AREG exposure significantly promoted hDPSC differentiation, shown by increased mineralized nodule formation and the expression of odontoblastic marker protein expression. In vivo micro-CT imaging and quantitative analysis showed significantly greater formation of highly mineralized tissue in the 0.1 μg/mL AREG exposure group in DPSC/NF-gelatin-scaffold composites. AREG also promoted extracellular matrix production, with collagen fiber, mineralized matrix, and calcium salt deposition on the composites, as shown by H&E, Masson, and Von Kossa staining. Furthermore, AREG overexpression boosted hDPSC differentiation while AREG silencing inhibited it. During the differentiation of hDPSCs, AREG treatment led to phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and PI3K/Akt. Notably, a specific inhibitor of ERK, JNK, and PI3K/Akt signaling markedly reduced AREG-induced differentiation, as well as levels of phosphorylated ERK and JNK in hDPSCs. Conclusions The data indicated that AREG promoted odontoblastic differentiation and facilitated regeneration and mineralization processes in hDPSCs. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02971-4.
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Affiliation(s)
- Junqing Li
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China.,Hospital of Stomatology, Zunyi Medical University, 89 Wu-jiang Dong Road, Zunyi, 563003, People's Republic of China
| | - Zhihua Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China
| | - Juan Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China
| | - Qian Guo
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China
| | - Yi Fu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China.,Hospital of Stomatology, Zunyi Medical University, 89 Wu-jiang Dong Road, Zunyi, 563003, People's Republic of China
| | - Zihan Dai
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China
| | - Minghao Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China
| | - Yu Bai
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China
| | - Xin Liu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, 145 Chang-le Road, Xi'an, 710032, People's Republic of China
| | - Paul R Cooper
- Department of Oral Sciences, Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Te Whare Wānanga O Otāgo, PO Box 56, Dunedin, 9054, New Zealand
| | - Jiayuan Wu
- Hospital of Stomatology, Zunyi Medical University, 89 Wu-jiang Dong Road, Zunyi, 563003, People's Republic of China.
| | - Wenxi He
- Department of Stomatology, Air Force Medical Center, Air Force Medical University, 30 Fucheng Road, Beijing, 100142, People's Republic of China.
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Shan P, Wang X, Zhang Y, Teng Z, Zhang Y, Jin Q, Liu J, Ma J, Nie X. P75 neurotrophin receptor positively regulates the odontogenic/osteogenic differentiation of ectomesenchymal stem cells via nuclear factor kappa-B signaling pathway. Bioengineered 2022; 13:11201-11213. [PMID: 35485233 PMCID: PMC9208484 DOI: 10.1080/21655979.2022.2063495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/24/2022] [Accepted: 04/01/2022] [Indexed: 11/02/2022] Open
Abstract
p75NTR, a neural crest stem cell marker, is continuously expressed in mesenchymal cells during tooth development. Importantly, high expression of p75NTR in the late bell stage implicates its involvement in odontogenesis and mineralization. However, the regulatory mechanisms underlying p75NTR involvement in odonto/osteogenic differentiation remain unclear. Here, we investigate the effect and potential mechanisms underlying p75NTR involvement in odonto/osteogenic differentiation. We dissected EMSCs from the first branchial arches of mice embryo and compared the proliferation and migration of p75NTR+/+ and p75NTR-/-EMSCs by transwell, scratch and cell counting kit 8(CCK8)assays. The differentiation ability and the involvement of nuclear factor kappa-B (NF-κB) pathway were investigated through alkaline phosphatase and immunofluorescence assay, real-time PCR, and western blot. During induction of dental epithelium conditioned medium, p75NTR+/+ EMSCs exhibited deeper Alkaline phosphatase (ALP) staining and higher expression of odonto/osteogenic genes/proteins (e.g., dentin sialoprotein (DSPP) than p75NTR+/+ EMSCs. Moreover, p75NTR+/+ EMSCs exhibited higher nuclear P65 expression than p75NTR-/-EMSCs. Inhibition of NF-κB pathway with Bay11-7082 in p75NTR+/+EMSCs substantially decreased DSPP expression level. However, activation of NF-κB pathway with Bay11-7082 in p75NTR-/-EMSCs enhanced DSPP expression level. Thus, p75NTR possibly plays a paramount role in the proliferation and differentiation of EMSCs via NF-κB pathway.
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Affiliation(s)
- Peifen Shan
- Department of Prosthodontics, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Xiaole Wang
- Department of Nursing, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Yanyan Zhang
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Zhisheng Teng
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Yunxiao Zhang
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Qiu Jin
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Jiefan Liu
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Jianfeng Ma
- Department of Prosthodontics, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
| | - Xin Nie
- Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China
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18
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Xiao J, Zheng Y, Zhang W, Zhang Y, Cao P, Liang Y, Bao L, Shi S, Feng X. General Control Nonrepressed Protein 5 Modulates Odontogenic Differentiation Through NF-κB Pathway in Tumor Necrosis Factor-α-Mediated Impaired Human Dental Pulp Stem Cells. Cell Reprogram 2022; 24:95-104. [PMID: 35172106 DOI: 10.1089/cell.2021.0113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Dental pulp stem cells (DPSCs) from pulpitis patients showed defective osteogenic differentiation. However, as the most well-studied histone acetyltransferase, the impaired general control nonrepressed protein 5 (GCN5) plays essential roles in various developmental processes. The aim of this study was to investigate the effect of GCN5 on DPSCs odontogenic differentiation. The healthy dental pulp tissues were obtained from the extracted impacted third molar of patients with the informed consent. DPSCs were treated with a high concentration of tumor necrosis factor-alpha (TNF-α) (100 ng/mL) and odontogenic differentiation-related gene and GCN5 protein level by Western blot analysis. Proliferation of the DPSCs was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunofluorescence staining detected GCN5 and NF-κB signaling for p-p65. The mechanism of GCN5 regulating odontogenic differentiation of DPSCs was determined by small interfering RNA analysis. Our data suggested that TNF-α can significantly reduce mineralization and the expression of dentin matrix acidic phosphoprotein 1 and dentin sialophosphoprotein at higher concentration (100 ng/mL). Meanwhile, it showed that the inflammation in microenvironment resulted in a downregulation of GCN5 expression and GCN5 knockdown caused decreased odontogenic differentiation of DPSCs was also found. In addition, the knockdown of GCN5 increased the expression of phosphorylation of p65, thus activating NF-κB pathway of DPSCs. Meanwhile, NF-κB pathway inhibitor pyrrolidinedithiocarbamic acid reversed the siGCN5 decreased odontogenic differentiation of DPSCs. Altogether, our findings indicated that in inflammatory microenvironments GCN5 plays a protective role in pulpitis impaired odontogenic differentiation of DPSCs by activating NF-κB pathway, which may provide a potential approach to dentin regeneration.
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Affiliation(s)
- Jingwen Xiao
- Department of Stomatology, Haimen District People's Hospital, Nantong, China
| | - Ya Zheng
- Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China
| | - Wei Zhang
- Department of Stomatology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Ye Zhang
- Jiangsu Vocational College of Medicine, Yancheng, China
| | - Peipei Cao
- Nantong Boyue Dentistry Out-patient Department, Nantong, China
| | - Yi Liang
- Department of Stomatology, Shanghai East Hospital Affiliated with Tongji University, Shanghai, China
| | - Liuliu Bao
- Department of Stomatology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Suping Shi
- Department of Stomatology, Haimen District People's Hospital, Nantong, China
| | - Xingmei Feng
- Department of Stomatology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
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19
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Sun XF, Qiao WW, Meng LY, Bian Z. PIEZO1 Ion Channels Mediate Mechanotransduction in Odontoblasts. J Endod 2022; 48:749-758. [DOI: 10.1016/j.joen.2022.02.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 01/30/2022] [Accepted: 02/07/2022] [Indexed: 12/21/2022]
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20
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Zhang SY, Ren JY, Yang B. Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration. World J Stem Cells 2021; 13:1625-1646. [PMID: 34909115 PMCID: PMC8641023 DOI: 10.4252/wjsc.v13.i11.1625] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/14/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) have attracted intense interest in the field of dental tissue regeneration. Dental tissue is a popular source of MSCs because MSCs can be obtained with minimally invasive procedures. MSCs possess distinct inherent properties of self-renewal, immunomodulation, proangiogenic potential, and multilineage potency, as well as being readily available and easy to culture. However, major issues, including poor engraftment and low survival rates in vivo, remain to be resolved before large-scale application is feasible in clinical treatments. Thus, some recent investigations have sought ways to optimize MSC functions in vitro and in vivo. Currently, priming culture conditions, pretreatment with mechanical and physical stimuli, preconditioning with cytokines and growth factors, and genetic modification of MSCs are considered to be the main strategies; all of which could contribute to improving MSC efficacy in dental regenerative medicine. Research in this field has made tremendous progress and continues to gather interest and stimulate innovation. In this review, we summarize the priming approaches for enhancing the intrinsic biological properties of MSCs such as migration, antiapoptotic effect, proangiogenic potential, and regenerative properties. Challenges in current approaches associated with MSC modification and possible future solutions are also indicated. We aim to outline the present understanding of priming approaches to improve the therapeutic effects of MSCs on dental tissue regeneration.
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Affiliation(s)
- Si-Yuan Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Yin Ren
- Department of Oral Radiology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Yang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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21
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Huang X, Li Z, Liu A, Liu X, Guo H, Wu M, Yang X, Han B, Xuan K. Microenvironment Influences Odontogenic Mesenchymal Stem Cells Mediated Dental Pulp Regeneration. Front Physiol 2021; 12:656588. [PMID: 33967826 PMCID: PMC8100342 DOI: 10.3389/fphys.2021.656588] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/23/2021] [Indexed: 12/21/2022] Open
Abstract
Dental pulp as a source of nutrition for the whole tooth is vulnerable to trauma and bacterial invasion, which causes irreversible pulpitis and pulp necrosis. Dental pulp regeneration is a valuable method of restoring the viability of the dental pulp and even the whole tooth. Odontogenic mesenchymal stem cells (MSCs) residing in the dental pulp environment have been widely used in dental pulp regeneration because of their immense potential to regenerate pulp-like tissue. Furthermore, the regenerative abilities of odontogenic MSCs are easily affected by the microenvironment in which they reside. The natural environment of the dental pulp has been proven to be capable of regulating odontogenic MSC homeostasis, proliferation, and differentiation. Therefore, various approaches have been applied to mimic the natural dental pulp environment to optimize the efficacy of pulp regeneration. In addition, odontogenic MSC aggregates/spheroids similar to the natural dental pulp environment have been shown to regenerate well-organized dental pulp both in preclinical and clinical trials. In this review, we summarize recent progress in odontogenic MSC-mediated pulp regeneration and focus on the effect of the microenvironment surrounding odontogenic MSCs in the achievement of dental pulp regeneration.
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Affiliation(s)
- Xiaoyao Huang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Zihan Li
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Anqi Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xuemei Liu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Hao Guo
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Meiling Wu
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Xiaoxue Yang
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Bing Han
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.,National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, China.,Shaanxi Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
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22
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Artemisinin protects DPSC from hypoxia and TNF-α mediated osteogenesis impairments through CA9 and Wnt signaling pathway. Life Sci 2021; 277:119471. [PMID: 33811898 DOI: 10.1016/j.lfs.2021.119471] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 03/19/2021] [Accepted: 03/27/2021] [Indexed: 02/08/2023]
Abstract
Dental pulp stem cells (DPSCs) possess the ability of multi-lineage differentiation, and are excellent sources of tissue engineering and regenerative medicine. Oxygen concentration and inflammation are two critical environmental factors that affect the osteogenic differentiation of DPSCs. We aimed to study the role of the antimalarial drug artemisinin on the osteogenic differentiation of human DPSCs under the hypoxia and inflammation conditions. We demonstrated that hypoxia (5% O2) and inflammation (20 ng/mL TNF-α), alone or in combination, significantly diminished in vitro cell survival and increased apoptotic rates. Notably, hypoxia and TNF-α exerted accumulative effect in suppressing the osteogenic differentiation of DPSCs, as evidenced by reduced expression levels of osteogenesis-associated genes including ALP, RUNX2 and OCN in osteogenic condition, as well as reduced mineral nodules formation as indicated by alizarin red staining. Artemisinin at the dose of 40 μM markedly reversed the suppression in cell survival caused by hypoxia or inflammation, and reduced apoptotic rates and the expressions of pro-apoptotic proteins. Additionally, artemisinin restored osteogenic differentiation of DPSCs under the hypoxia or/and inflammation conditions. Moreover, the beneficial effect of artemisinin was dependent on upregulated expression of CA9 and CA9-mediated antioxidant responses, as CA9 knockdown abolished the protective role of artemisinin on DPSC osteogenesis. Furthermore, while hypoxia or/and inflammation significantly inactivated the Wnt/β-catenin signaling in DPSCs, additional exposure to artemisinin re-activated this pathway to promote osteogenic differentiation of DPSCs. Our results provide novel insight on the link between artemisinin and DPSC osteogenesis, and suggest promising artemisinin-based strategies for better dentin/pulp tissue engineering.
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23
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Luo M, Zhao F, Liu L, Yang Z, Tian T, Chen X, Cao X, Chen D, Chen X. IFN-γ/SrBG composite scaffolds promote osteogenesis by sequential regulation of macrophages from M1 to M2. J Mater Chem B 2021; 9:1867-1876. [DOI: 10.1039/d0tb02333g] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The macrophage-dominated bone immune response plays an important role in osteogenesis of bone defects.
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Affiliation(s)
- Man Luo
- Department of Biomedical Engineering
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou
- China
| | - Fujian Zhao
- Stomatological Hospital
- Southern Medical University
- Guangzhou 510280
- China
| | - Lu Liu
- Department of Biomedical Engineering
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou
- China
| | - Zhen Yang
- Department of Biomedical Engineering
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou
- China
| | - Ting Tian
- National Engineering Research Center for Tissue Restoration and Reconstruction
- Guangzhou
- China
- Key Laboratory of Biomedical Engineering of Guangdong Province
- South China University of Technology
| | - Xiaoyu Chen
- Department of Biomedical Engineering
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou
- China
| | - Xiaodong Cao
- Department of Biomedical Engineering
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou
- China
| | - Dafu Chen
- Laboratory of Bone Tissue Engineering
- Beijing Laboratory of Biomedical Materials
- Beijing Research Institute of Orthopaedics and Traumatology
- Beijing JiShuiTan Hospital
- Beijing
| | - Xiaofeng Chen
- Department of Biomedical Engineering
- School of Materials Science and Engineering
- South China University of Technology
- Guangzhou
- China
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24
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Nam OH, Lee HS, Kim JH, Chae YK, Hong SJ, Kang SW, Lee HS, Choi SC, Kim Y. Differential Gene Expression Changes in Human Primary Dental Pulp Cells Treated with Biodentine and TheraCal LC Compared to MTA. Biomedicines 2020; 8:biomedicines8110445. [PMID: 33105546 PMCID: PMC7690278 DOI: 10.3390/biomedicines8110445] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/16/2020] [Accepted: 10/20/2020] [Indexed: 12/14/2022] Open
Abstract
This study aimed to analyze the effects of pulp capping materials on gene expression changes in primary tooth-derived dental pulp cells using next-generation sequencing. Dental pulp cells were extracted and treated with mineral trioxide aggregate (MTA), Biodentine (BD), or TheraCal LC (TC). Cell viability assays were performed. Total RNA was extracted and analyzed through mRNA sequencing. Bioinformatic analysis of differential gene expression in dental pulp cells exposed to BD or TC versus MTA was performed. MTA, BD, and TC exposure had no significant effect on pulp cell viability (p > 0.05). Gene sets associated with inflammatory response (p = 2.94 × 10−5) and tumor necrosis factor alpha (TNF-α) signaling via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (p = 2.94 × 10−5) were enriched in all materials. In BD-treated cells, Wnt/β-catenin signaling (p = 3.15 × 10−4) gene sets were enriched, whereas enrichment of interferon gamma (IFN-γ) response (p = 3 × 10−3) was observed in TC-treated cells. In gene plot analysis, marked increases in receptor activator of nuclear factor kappa-Β ligand (RANKL) expression were seen in TC-treated cells over time. Despite the similar cell viabilities exhibited among MTA-, BD-, and TC-treated cells, patterns of gene networks differed, suggesting that diverse functional gene differences may be associated with treatment using these materials.
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Affiliation(s)
- Ok Hyung Nam
- Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
| | - Ho Sun Lee
- Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
| | - Jae-Hwan Kim
- Department of Pediatric Dentistry, School of Dentistry, Jeonbuk National University, Jeonju 54896, Korea
| | - Yong Kwon Chae
- Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
| | - Seoung-Jin Hong
- Department of Prosthodontics, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
| | - Sang Wook Kang
- Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
| | - Hyo-Seol Lee
- Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
| | - Sung Chul Choi
- Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul 02447, Korea
| | - Young Kim
- Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju 61186, Korea
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25
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Huang H, Li X, Wang Z, Lin X, Tian Y, Zhao Q, Zheng P. Anti-inflammatory effect of selenium on lead-induced testicular inflammation by inhibiting NLRP3 inflammasome activation in chickens. Theriogenology 2020; 155:139-149. [PMID: 32673849 DOI: 10.1016/j.theriogenology.2020.06.015] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/01/2020] [Accepted: 06/13/2020] [Indexed: 12/18/2022]
Abstract
Lead (Pb) is a deleterious environmental pollutant that is toxic to testes. Selenium (Se) possesses antioxidant and anti-inflammatory properties. Nucleotide-binding domain, leucine-rich-containing family, pyrin-domain containing-3 (NLRP3) inflammasome is involved in inflammatory response. However, the function of NLRP3 inflammasome in antagonistic effect of Se on inflammation caused by Pb remains unknown. The purpose of this research is to identify anti-inflammatory role of Se on testicular toxicity induced by Pb with an emphasis on oxidative stress, inflammation and NLRP3 signaling pathway in chicken. In present study, sixty seven-day-old Hyline male chickens were assigned into four groups. The feeding program consisted of a commercial diet (0.49 mg/kg Se), a Se-supplemented diet (1 mg/kg Se), a Pb-supplemented diet (0.49 mg/kg Se and 350 mg/kg Pb) and a Se-supplemented and Pb-supplemented diet (1 mg/kg Se and 350 mg/kg Pb), respectively. On the 12th week, blood was collected to measure serum testosterone level and testicular tissues were removed to determine Se and Pb concentrations, testicular function, histological structure, oxidative stress indicators and inflammation-related factors (Nuclear factor-kappaB, tumor necrosis factor-α, cyclooxygenase-2, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, interluekin (IL)-1β, IL-6, IL-18 and interferon-γ). The experimental results showed that after Pb administration, testicular injury was confirmed via histological assessment; testicular dysfunction were further indicated by decreased testosterone level and mRNA expression of steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase. Moreover, NLRP3 signaling pathway activated by Pb-caused oxidative stress was up-regulated accompanied by promotion in reactive oxygen species, nitric oxide, inducible nitric oxide synthase and malondialdehyde and reduction in antioxidants including glutathione peroxidase and glutathione s-transferase. Se administration ameliorated testicular tissue injury, testicular function, oxidative stress and inflammation. In conclusion, Se exhibited antagonistic role in Pb-induced testicular injury via enhancing antioxidant system and inhibiting inflammation in chickens.
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Affiliation(s)
- He Huang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Xiaoyu Li
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Ziming Wang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Xu Lin
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Yaguang Tian
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China
| | - Qian Zhao
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
| | - Peng Zheng
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, People's Republic of China.
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26
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Dhanushkodi NR, Srivastava R, Prakash S, Roy S, Coulon PGA, Vahed H, Nguyen AM, Salazar S, Nguyen L, Amezquita C, Ye C, Nguyen V, BenMohamed L. High Frequency of Gamma Interferon-Producing PLZF loRORγt lo Invariant Natural Killer 1 Cells Infiltrating Herpes Simplex Virus 1-Infected Corneas Is Associated with Asymptomatic Ocular Herpesvirus Infection. J Virol 2020; 94:e00140-20. [PMID: 32102882 PMCID: PMC7163123 DOI: 10.1128/jvi.00140-20] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 02/13/2020] [Indexed: 12/12/2022] Open
Abstract
Invariant natural killer (iNKT) cells are among the first innate immune cells to elicit early protective immunity that controls invading viral pathogens. The role of the iNKT cell subsets iNKT1, iNKT2, and iNKT17 in herpesvirus immunity remains to be fully elucidated. In this study, we examined the protective role of cornea-resident iNKT cell subsets using the mouse model of ocular herpesvirus infection and disease. Wild-type (WT) C57BL/6 (B6) mice and CD1d knockout (KO) mice were infected ocularly with herpes simplex virus 1 (HSV-1) (strain McKrae). Cornea, spleen, and liver were harvested at 0, 2, 5, 8, and 14 days postinfection (p.i.), and the frequency and function of the three major iNKT cell subsets were analyzed and correlated with symptomatic and asymptomatic corneal herpesvirus infections. The profiles of 16 major pro- and anti-inflammatory cytokines were analyzed in corneal lysates using Western blot and Luminex assays. Early during ocular herpesvirus infection (i.e., day 2), the gamma interferon (IFN-γ)-producing PLZFloRORγtlo (promyelocytic leukemia zinc finger, retinoic acid-related orphan receptor gT) iNKT1 cell subset was the predominant iNKT cell subset in infected asymptomatic corneas. Moreover, compared to the asymptomatic corneas of HSV-1-infected WT mice, the symptomatic corneas CD1d KO mice, with iNKT cell deficiency, had increased levels of the inflammatory cytokine interleukin-6 (IL-6) and decreased levels of IL-12, IFN-γ, and the JAK1, STAT1, NF-κB, and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways. Our findings suggest that IFN-γ-producing PLZFloRORγtlo iNKT1 cells play a role in the protective innate immune response against symptomatic ocular herpes.IMPORTANCE We investigated the protective role of iNKT cell subsets in asymptomatic ocular herpesvirus infection. We found that early during ocular herpesvirus infection (i.e., on day 2 postinfection), IFN-γ-producing PLZFloRORγtlo iNKT1 cells were the predominant iNKT cell subset in infected corneas of asymptomatic B6 mice (with little to no corneal herpetic disease), compared to corneas of symptomatic mice (with severe corneal herpetic disease). Moreover, compared to asymptomatic corneas of wild-type (WT) B6 mice, the symptomatic corneas of CD1d KO mice, which lack iNKT cells, showed (i) decreases in the levels of IFN-γ and IL-12, (ii) an increase in the level of the inflammatory cytokine IL-6; and (iii) downregulation of the JAK1, STAT1, NF-κB, and ERK1/2 pathways. The findings suggest that early during ocular herpesvirus infection, cornea-resident IFN-γ-producing PLZFloRORγtlo iNKT1 cells provide protection from symptomatic ocular herpes.
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Affiliation(s)
- Nisha R Dhanushkodi
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Ruchi Srivastava
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Swayam Prakash
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Soumyabrata Roy
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Pierre-Gregoire A Coulon
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Hawa Vahed
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Angela M Nguyen
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Stephanie Salazar
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Lan Nguyen
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Cassandra Amezquita
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Caitlin Ye
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Vivianna Nguyen
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Lbachir BenMohamed
- Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA
- Department of Molecular Biology and Biochemistry, University of California, Irvine, School of Medicine, Irvine, California, USA
- Institute for Immunology, University of California, Irvine, School of Medicine, Irvine, California, USA
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27
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Mesenchymal Stem Cells from Human Exfoliated Deciduous Teeth and the Orbicularis Oris Muscle: How Do They Behave When Exposed to a Proinflammatory Stimulus? Stem Cells Int 2020; 2020:3670412. [PMID: 32184831 PMCID: PMC7060870 DOI: 10.1155/2020/3670412] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 01/04/2020] [Accepted: 02/01/2020] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem cells (MSCs) have been studied as a promising type of stem cell for use in cell therapies because of their ability to regulate the immune response. Although they are classically isolated from the bone marrow, many studies have sought to isolate MSCs from noninvasive sources. The objective of this study was to evaluate how MSCs isolated from the dental pulp of human exfoliated deciduous teeth (SHED) and fragments of the orbicularis oris muscle (OOMDSCs) behave when treated with an inflammatory IFN-γ stimulus, specifically regarding their proliferative, osteogenic, and immunomodulatory potentials. The results demonstrated that the proliferation of SHED and OOMDSCs was inhibited by the addition of IFN-γ to their culture medium and that treatment with IFN-γ at higher concentrations resulted in a greater inhibition of the proliferation of these cells than treatment with IFN-γ at lower concentrations. SHED and OOMDSCs maintained their osteogenic differentiation potential after stimulation with IFN-γ. Additionally, SHED and OOMDSCs have been shown to have low immunogenicity because they lack expression of HLA-DR and costimulatory molecules such as CD40, CD80, and CD86 before and after IFN-γ treatment. Last, SHED and OOMDSCs expressed the immunoregulatory molecule HLA-G, and the expression of this antigen increased after IFN-γ treatment. In particular, an increase in intracellular HLA-G expression was observed. The results obtained suggest that SHED and OOMDSCs lack immunogenicity and have immunomodulatory properties that are enhanced when they undergo inflammatory stimulation with IFN-γ, which opens new perspectives for the therapeutic use of these cells.
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28
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Wang J, Du Y, Deng J, Wang X, Long F, He J. MicroRNA-506 Is Involved in Regulation of the Occurrence of Lipopolysaccharides (LPS)-Induced Pulpitis by Sirtuin 1 (SIRT1). Med Sci Monit 2019; 25:10008-10015. [PMID: 31877121 PMCID: PMC6944165 DOI: 10.12659/msm.918172] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Toothache often occurs with pulpitis. Lipopolysaccharide (LPS) is produced by gram-negative bacteria, and its accumulation is related to clinical symptoms of pain. MicroRNAs (miRNAs) display anti-inflammatory potential due to their direct regulation of cellular protein expression, which can promote inflammatory changes in dental pulp tissues. However, the mechanism of LPS-induced pulpitis is still unclear. Material/Methods In this study, dental pulp stem cells (DPSCs) were separated and cultured from rat dental pulp tissues; then, LPS was administered to induce inflammation and activate the TLR4 pathway. Results It was found that miR-506 was upregulated following LPS treatment in DPSCs. The inhibition of miR-506 in LPS-treated DPSCs led to attenuated inflammation and deactivation of the TLR4 pathway. Furthermore, the bioinformatic analysis and dual-luciferase reporter gene assay indicated that miR-506 could target the 3′-UTR of sirtuin 1 (SIRT1). Additionally, SIRT1 decreased in LPS-treated DPSCs, and miR-506 transfection resulted in SIRT1 upregulation. SIRT1 overexpression showed a similar inhibitory effect as that of miR-506 downregulation on inflammation and TLR4 activation in DPSCs. Conclusions In brief, miR-506 can protect dental pulp in LPS-induced inflammation by inhibiting the SIRT1-mediated TLR4 pathway.
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Affiliation(s)
- Jun Wang
- Stomatological Center, Gansu Provincial Hospital, Lanzhou, Gansu, China (mainland)
| | - Yi Du
- Department of Nursing, The First Hospital of Lanzhou University, Lanzhou, Gansu, China (mainland)
| | - Junhong Deng
- Department of Stomatology, The Second People's Hospital of Lanzhou City, Lanzhou, Gansu, China (mainland)
| | - Xin Wang
- Departments of Health and Social Care, The Second People's Hospital of Lanzhou City, Lanzhou, Gansu, China (mainland)
| | - Fei Long
- Stomatological Center, Gansu Provincial Hospital, Lanzhou, Gansu, China (mainland)
| | - Jianmin He
- Stomatological Center, Gansu Provincial Hospital, Lanzhou, Gansu, China (mainland)
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29
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Avtanski D, Garcia A, Caraballo B, Thangeswaran P, Marin S, Bianco J, Lavi A, Poretsky L. In vitro effects of resistin on epithelial to mesenchymal transition (EMT) in MCF-7 and MDA-MB-231 breast cancer cells - qRT-PCR and Westen blot analyses data. Data Brief 2019; 25:104118. [PMID: 31417946 PMCID: PMC6690660 DOI: 10.1016/j.dib.2019.104118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Revised: 05/22/2019] [Accepted: 05/29/2019] [Indexed: 11/09/2022] Open
Abstract
Resistin is an adipokine produced by the white adipocytes and adipose-derived macrophages, which mediates inflammation and insulin resistance Huang et al., 1997 and Renehan et al., 2008 Feb. Here, we provide data on the effect of resistin on epithelial to mesenchymal transition (EMT) in breast cancer cells in vitro. As model systems, we used human MCF-7 (low-metastatic) and MDA-MB-231 (high-metastatic) breast cancer cell lines. To optimize experimental conditions, we treated the cells with various concentrations of resistin (12.5, 25 and 50 ng/ml) for different time intervals (6 and 24 hours), and measured SOCS3 mRNA expression by using qRT-PCR analysis. Further, we used qRT-PCR and Western blot analyses to measure the expression of various epithelial (E-cadherin, claudin-1) and mesenchymal (SNAIL, SLUG, ZEB1, TWIST1, fibronectin, and vimentin) markers after resistin treatment. This data article is part of a study Avtanski et al., 2019 May, where detailed interpretation and discussion can be found.
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Affiliation(s)
- Dimiter Avtanski
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
- The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
| | - Anabel Garcia
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Beatriz Caraballo
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Priyanthan Thangeswaran
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Sela Marin
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Julianna Bianco
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Aaron Lavi
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Leonid Poretsky
- Gerald J. Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, New York, NY, USA
- The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
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Yunnan Baiyao Conditioned Medium Promotes the Odonto/Osteogenic Capacity of Stem Cells from Apical Papilla via Nuclear Factor Kappa B Signaling Pathway. BIOMED RESEARCH INTERNATIONAL 2019; 2019:9327386. [PMID: 31179335 PMCID: PMC6507233 DOI: 10.1155/2019/9327386] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 03/27/2019] [Indexed: 02/04/2023]
Abstract
Yunnan Baiyao is a traditional Chinese herbal remedy that has long been used for its characteristics of wound healing, bone regeneration, and anti-inflammation. However, the effects of Yunnan Baiyao on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) and the potential mechanisms remain unclear. The aim of this study was to investigate the odonto/osteogenic differentiation effects of Yunnan Baiyao on SCAPs and the underlying mechanisms involved. SCAPs were isolated and cocultured with Yunnan Baiyao conditioned media. The proliferation ability was determined by cell counting kit 8 and flow cytometry. The differentiation capacity and the involvement of NF-κB pathway were investigated by alkaline phosphatase assay, alizarin red staining, immunofluorescence assay, real-time RT-PCR, and western blot analyses. Yunnan Baiyao conditioned medium at the concentration of 50 μg/mL upregulated alkaline phosphatase activity, induced more mineralized nodules, and increased the expression of odonto/osteogenic genes/proteins (e.g., OCN/OCN, OPN/OPN, OSX/OSX, RUNX2/RUNX2, ALP/ALP, COL-I/COL-I, DMP1, DSP/DSPP) of SCAPs. In addition, the expression of cytoplasmic phos-IκBα, phos-P65, and nuclear P65 was significantly increased in Yunnan Baiyao conditioned medium treated SCAPs in a time-dependent manner. Conversely, the differentiation of Yunnan Baiyao conditioned medium treated SCAPs was obviously inhibited when these stem cells were cocultured with the specific NF-κB inhibitor BMS345541. Yunnan Baiyao can promote the odonto/osteogenic differentiation of SCAPs via the NF-κB signaling pathway.
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Kim HJ, Kim HJ, Kim MK, Bae MK, Sung HY, Ahn JH, Kim YH, Kim SC, Ju W. SPSB1 enhances ovarian cancer cell survival by destabilizing p21. Biochem Biophys Res Commun 2019; 510:364-369. [PMID: 30712944 DOI: 10.1016/j.bbrc.2019.01.088] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 01/19/2019] [Indexed: 11/20/2022]
Abstract
SPRY domain-containing SOCS box protein 1 (SPSB1) is an E3 ligase adaptor protein with unknown functions in cancer cells. In this study, we found that SPSB1 knockdown markedly decreased the viability and migration of ovarian cancer cells, while ectopic SPSB1 overexpression in IL-3-dependent Ba/F3 cells significantly increased their proliferation rate compared with empty vector-transfected cells. SPSB1 knockdown significantly elevated p21 protein and mRNA levels and induced apoptosis in ovarian cancer cells, as evidenced by increased levels of cleaved PARP and decreased levels of Bcl-2. Notably, mechanistic investigations revealed that SPSB1 accelerated p21 destabilization by directly interacting with p21 and promoting its ubiquitin-mediated proteasomal degradation. Taken together, our findings provide novel insights into the role of SPSB1 in ovarian cancer cells.
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Affiliation(s)
- Hyun-Jung Kim
- Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea
| | - Hye Jin Kim
- Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea
| | - Mi-Kyung Kim
- Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea
| | - Moon Kyoung Bae
- Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea
| | - Hye Youn Sung
- Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea
| | - Jung-Hyuck Ahn
- Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea
| | - Yun Hwan Kim
- Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea
| | - Seung Cheol Kim
- Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea
| | - Woong Ju
- Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, Seoul, South Korea; Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, South Korea.
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Yuan H, Zhao H, Wang J, Zhang H, Hong L, Li H, Che H, Zhang Z. MicroRNA let-7c-5p promotes osteogenic differentiation of dental pulp stem cells by inhibiting lipopolysaccharide-induced inflammation via HMGA2/PI3K/Akt signal blockade. Clin Exp Pharmacol Physiol 2019; 46:389-397. [PMID: 30575977 DOI: 10.1111/1440-1681.13059] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 12/13/2018] [Accepted: 12/17/2018] [Indexed: 12/20/2022]
Abstract
Pulpitis suppressed the level of let-7c-5p that promotes osteogenesis and bone formation by repressing HMGA2. In the current study, the function of let-7c-5p in the inflammation and osteogenesis in dental pulp stem cells (DPSCs) was explored. The level of let-7c-5p in DPSCs was up-regulated, and the cells were subjected to lipopolysaccharide (LPS) to induce inflammation. The effect of let-7c-5p on cell proliferation potential, osteogenic differentiation potential, and activity of HMGA2/PI3K/Akt pathway was detected. The administration of LPS suppressed the cell proliferation of DPSCs and suppressed calcium deposition, activity of alkaline phosphatase (ALP), and levels of OCN, OPN, OSX, MSX2, and RUNX2 in inflamed DPSCs. The impaired osteogenic differentiation of inflamed DPSCs was associated with the increased levels of HMGA2, p-PI3K, and p-Akt. In let-7c-5p-overexpressed inflamed DPSCs, the proliferation and osteogenic differentiation potential of DPSCs were restored, and the activation of HMGA2/PI3K/Akt signalling was inhibited. In rat pulpitis models, the injection of let-7c-5p agomir restored the osteogenic differentiation potential of dental pulp cells and inhibited HMGA2/PI3K/Akt signalling. The findings demonstrated the anti-inflammation and pro-osteogenesis effect of let-7c-5p during the attack of pulpitis, which depended on the inhibition of HMGA2/PI3K/Akt signalling.
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Affiliation(s)
- Hao Yuan
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
| | - Hongyan Zhao
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
| | - Jiafeng Wang
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
| | - Hong Zhang
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
| | - Lihua Hong
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
| | - He Li
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
| | - Hongze Che
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
| | - Zhimin Zhang
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, China
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Guanylate-Binding Protein 1 Promotes Migration and Invasion of Human Periodontal Ligament Stem Cells. Stem Cells Int 2019; 2018:6082956. [PMID: 30622567 PMCID: PMC6304207 DOI: 10.1155/2018/6082956] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 08/18/2018] [Accepted: 09/18/2018] [Indexed: 12/13/2022] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are capable of migrating to sites of injury and inflammation in response to various cytokines to improve tissue repair. Previous studies have shown interferon-gamma (IFN-γ) promoted migration of the V54/2 cell line and dental pulp stem cells (DPSCs), but the underlying mechanisms remain largely unknown. In this study, we found IFN-γ induced migration and invasion of periodontal ligament stem cells (PDLSCs) in a dose-dependent manner in vitro. While knockdown of guanylate-binding protein 1 (GBP1) suppressed IFN-γ-induced migration and invasion, ectopic expression of GBP1 potentiated IFN-γ-induced migration and invasion of PDLSCs. Furthermore, we demonstrated GBP1 was required for IFN-γ-induced processing of matrix metallopeptidase 2 (MMP2) in PDLSCs. Our findings indicate that GBP1 promotes IFN-γ-induced migration and invasion of PDLSCs by MMP2, and GBP1 may serve as a new target to facilitate MSC homing and migration.
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Li Y, Zheng Q, Sun D, Cui X, Chen S, Bulbul A, Liu S, Yan Q. Dehydroepiandrosterone stimulates inflammation and impairs ovarian functions of polycystic ovary syndrome. J Cell Physiol 2018; 234:7435-7447. [PMID: 30580448 DOI: 10.1002/jcp.27501] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 09/07/2018] [Indexed: 12/28/2022]
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. It is characterized by ovulation dysfunction, polycystic ovaries, and hyperandrogenism. Inflammation is likely to be a crucial contributor to the pathogenesis of PCOS. However, the association between the inflammatory cytokines and the development of PCOS has not been reported. To explore the relationship between the inflammatory cytokines and PCOS, alterations of serum proteins in dehydroepiandrosterone (DHEA)-induced PCOS rats were screened by protein array, and the concentration of IFN-γ was further measured by using enzyme-linked immunosorbent assay (ELISA). DHEA-induced PCOS rats had a decreased level of IFN-γ compared with the control rats, which was restored partly in flutamide (an androgen receptor antagonist)-treated rats. Moreover, the level of IFN-γ in serum of patients with PCOS was also lower than that in healthy women. Using the ovarian granulosa cells (KGN), we demonstrated that DHEA downregulated the expression and secretion of IFN-γ in dose- and time-dependent manners, which could be restored to some extent by treating with flutamide. Furthermore, flutamide ameliorated the inhibitory effect on cell proliferation and promotive effect on cell apoptosis by DHEA. The results also revealed that IFN-γ promoted the proliferation but inhibited the apoptosis of KGN cells, which was suppressed by DHEA via activating the downstream PI3K/AKT signaling pathway. Taken together, these results showed that DHEA inhibited the proliferation and promoted the apoptosis of ovarian granulosa cells through downregulating the expression of IFN-γ which could be restored by flutamide, and IFN-γ may serve as a potential inflammatory biomarker for PCOS detection.
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Affiliation(s)
- Yulin Li
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
| | - Qin Zheng
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
| | - Dan Sun
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
| | - Xinyuan Cui
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
| | - Siyi Chen
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
| | - Ahmmed Bulbul
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
| | - Shuai Liu
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
| | - Qiu Yan
- College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China
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Kukolj T, Trivanović D, Mojsilović S, Okić Djordjević I, Obradović H, Krstić J, Jauković A, Bugarski D. IL-33 guides osteogenesis and increases proliferation and pluripotency marker expression in dental stem cells. Cell Prolif 2018; 52:e12533. [PMID: 30430681 PMCID: PMC6430470 DOI: 10.1111/cpr.12533] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 08/03/2018] [Accepted: 08/28/2018] [Indexed: 12/12/2022] Open
Abstract
Objectives Soluble IL‐33 (interleukin (IL)‐1‐like cytokine) acts as endogenous alarm signal (alarmin). Since alarmins, besides activating immune system, act to restore tissue homeostasis, we investigated whether IL‐33 exerts beneficial effects on oral stem cell pull. Materials and Methods Clonogenicity, proliferation, differentiation and senescence of stem cells derived from human periodontal ligament (PDLSCs) and dental pulp (DPSCs) were determined after in vitro exposure to IL‐33. Cellular changes were detected by flow cytometry, Western blot, immunocytochemistry and semiquantitative RT‐PCR. Results IL‐33 stimulated proliferation, clonogenicity and expression of pluripotency markers, OCT‐4, SOX‐2 and NANOG, but it inhibited ALP activity and mineralization in both PDLSCs and DPSCs. Higher Ki67 expression and reduced β‐galactosidase activity in IL‐33‐treated cells were demonstrated, whereas these trends were more conspicuous in osteogenic medium. However, after 7‐day IL‐33 pretreatment, differentiation capacity of IL‐33‐pretreated cells was retained, and increased ALP activity was observed in both cell types. Results showed that IL‐33 regulates NF‐κB and β‐catenin signalling, indicating the association of these molecules with changes observed in IL‐33‐treated PDLSCs and DPSCs, particularly their proliferation, pluripotency‐associated marker expression and osteogenesis. Conclusions IL‐33 treatment impairs osteogenesis of PDLSCs and DPSCs, while increases their clonogenicity, proliferation and pluripotency marker expression. After exposure to IL‐33, osteogenic capacity of cells stayed intact. NF‐κB and β‐catenin are implicated in the effects achieved by IL‐33 in PDLSCs and DPSCs.
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Affiliation(s)
- Tamara Kukolj
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Drenka Trivanović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Slavko Mojsilović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Ivana Okić Djordjević
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Hristina Obradović
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Jelena Krstić
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Jauković
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
| | - Diana Bugarski
- Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia
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Yuan H, Zhang H, Hong L, Zhao H, Wang J, Li H, Che H, Zhang Z. MicroRNA let-7c-5p Suppressed Lipopolysaccharide-Induced Dental Pulp Inflammation by Inhibiting Dentin Matrix Protein-1-Mediated Nuclear Factor kappa B (NF-κB) Pathway In Vitro and In Vivo. Med Sci Monit 2018; 24:6656-6665. [PMID: 30238933 PMCID: PMC6162970 DOI: 10.12659/msm.909093] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Background Let-7c-5p is down-regulated in dental pulp tissues in inflammatory disorders. The microRNA (miR) molecule shows an anti-inflammation potential due to its direct regulation of dentin matrix protein-1 (DMP1), which promotes inflammation changes in dental pulp tissues. In the present study, the effect of let-7c-5p on lipopolysaccharide (LPS)-induced pulpitis was detected and the associated mechanism was explored. Material/Methods Dental pulp stem cells (DPSCs) were isolated from rat dental tissues, infected with let-7c-5p lentivirus particles, and subjected to LPS administration to induce inflammation. Then, the effect of let-7c-5p overexpression on LPS-induced impairments on DPSCs were detected and the mechanism was explained by focusing on the DMP1 expression and NF-κB pathway. The role of DMP1 in the anti-inflammation effect of let-7c-5p was assessed by incubating let-7c-5p-expressed DPSCs with DMP1 protein. The results of in vitro assays were verified in LPS-induced rat pulpitis models. Results LPS administration increased the production of IL-1β and TNF-α and decreased DPSCs viability by increasing the expression of DMP1 and activating NF-κB pathway. However, the induced expression of let-7c-5p relieved DPSCs from LPS-induced inflammation and suppressed DMP1 as well as NF-κB pathway. The incubation of let-7c-5p-expressed DPSCs with DMP1 protein blocked the effect of let-7c-5p. In in vivo experiments, the injection of let-7c-5p attenuated LPS-induced pulpitis by inhibiting DMP1-mediated NF-κB pathway. Conclusions Findings outlined in the current study demonstrated the dental pulp protecting function of let-7c-5p during LPS-induced inflammation, which was exerted by inhibiting the DMP1-mediated NF-κB pathway.
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Affiliation(s)
- Hao Yuan
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
| | - Hong Zhang
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
| | - Lihua Hong
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
| | - Hongyan Zhao
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
| | - Jiafeng Wang
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
| | - He Li
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
| | - Hongze Che
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
| | - Zhimin Zhang
- Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland)
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Liu M, Zhao L, Hu J, Wang L, Li N, Wu D, Shi X, Yuan M, Hu W, Wang X. Endothelial cells and endothelin‑1 promote the odontogenic differentiation of dental pulp stem cells. Mol Med Rep 2018; 18:893-901. [PMID: 29845193 PMCID: PMC6059721 DOI: 10.3892/mmr.2018.9033] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 04/13/2018] [Indexed: 12/14/2022] Open
Abstract
It has been established that dental pulp stem cells (DPSCs) serve an important role in the restoration and regeneration of dental tissues. DPSCs are present in blood vessels and also exist in the vessel microenvironment in vivo and have a close association with endothelial cells (ECs). The present study aimed to evaluate the influence of ECs and their secretory product endothelin-1 (ET-1) on the differentiation of DPSCs. In the present study, cells were divided into four groups: i) a DPSC-only control group; ii) a DPSC with ET-1 administration group; iii) a DPSC and human umbilical vein endothelial cell (HUVEC) direct co-culture group; and iv) a DPSC and HUVEC indirect co-culture group using a Transwell system. Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of the odontoblastic differentiation-associated genes, including dentin sialoprotein (DSP) and dentin matrix acidic phosphoprotein 1 (DMP-1) at days 4, 7, 14 and 21. Alizarin Red S staining, immunofluorescence and western blot analyses were also conducted to assess the differentiation of the DPSCs in each group. The highest expression levels of odontoblastic differentiation-associated genes were observed on day 7 and in the two co-culture groups were increased compared with the DPSC-only and DPSC + ET-1 culture groups at all four time points. However, expression levels in the DPSC + ET-1 group were not downregulated as notably as in the co-culture groups on days 14 and 21. The Transwell group exhibited the greatest ability for odontoblastic differentiation compared with the other groups according to staining with Alizarin Red S, immunofluorescence and western blot analysis results. According to the results of the present study, the culture solution with HUVECs affected the differentiation of DPSCs. In addition, ET-1 may promote the odontoblastic differentiation of DPSCs.
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Affiliation(s)
- Mingyue Liu
- Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Lin Zhao
- Department of Stomatology, Dezhou People's Hospital, Dezhou, Shandong 253000, P.R. China
| | - Junlong Hu
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Lihua Wang
- Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Ning Li
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Di Wu
- Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Xin Shi
- Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Mengtong Yuan
- Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Weiping Hu
- Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
| | - Xiaofeng Wang
- Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
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Zhang P, Yang W, Wang G, Li Y. miR-143 suppresses the osteogenic differentiation of dental pulp stem cells by inactivation of NF-κB signaling pathway via targeting TNF-α. Arch Oral Biol 2017; 87:172-179. [PMID: 29306073 DOI: 10.1016/j.archoralbio.2017.12.031] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 12/11/2017] [Accepted: 12/29/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND Dental pulp stem cells (DPSCs) are multipotent and play an important role in repairing damaged and/or defective dentinogenesis/osteogenesis. Recent studies have documented the implication of miR-143 in osteogenic differentiation of DPSCs. Nevertheless, the detailed mechanisms of miR-143 involved in the osteogenic differentiation of DPSCs remain to be further elaborated. METHODS Isolated DPSCs were incubated with osteogenic differentiation medium to induce osteogenic differentiation. qRT-PCR and western blot were performed to determine the expressions of miR-143 and tumor necrosis factor α (TNF-α). Luciferase reporter assay was used to confirm whether TNF-α was a target of miR-143. Osteogenic differentiation of DPSCs was evaluated by alkaline phosphatase (ALP) activity assay, ALP staining, and western blot analyses of osteogenic-markers including bone morphogenetic protein 2 (BMP2), ALP, runt-related transcription factor 2 (RUNX2) and collagen type I (COLI). RESULTS miR-143 was downregulated and TNF-α was upregulated during osteogenic differentiation of DPSCs. miR-143 posttranscriptionally regulated TNF-α expression in DPSCs by binding to its 3'UTR. miR-143 overexpression suppressed osteogenic differentiation of DPSCs, as demonstrated by the decrease of ALP activity, ALP positive cell ratio, as well as BMP2, ALP, RUNX2, and COLI expressions. Moreover, miR-143 reversed TNF-α-induced osteogenic differentiation of DPSCs. Finally, the osteogenic differentiation of DPSCs induced by miR-143 inhibitor was attenuated following inactivation of nuclear factor kappa B (NF-κB) signaling pathway. CONCLUSION miR-143 suppressed the osteogenic differentiation of DPSCs by blockade of NF-κB signaling pathway via targeting TNF-α.
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Affiliation(s)
- Peng Zhang
- Department of Prosthodontics, The First Affiliated Hospital & School of Stomatology, Zhengzhou University, No. 40 Daxue Road, Zhengzhou, 450052, China.
| | - Wenli Yang
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Guofang Wang
- Department of Periodontology, The First Affiliated Hospital & School of Stomatology, Zhengzhou University, Zhengzhou, 450052, China
| | - Yajing Li
- Department of Periodontology, The First Affiliated Hospital & School of Stomatology, Zhengzhou University, Zhengzhou, 450052, China
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Sui BD, Hu CH, Liu AQ, Zheng CX, Xuan K, Jin Y. Stem cell-based bone regeneration in diseased microenvironments: Challenges and solutions. Biomaterials 2017; 196:18-30. [PMID: 29122279 DOI: 10.1016/j.biomaterials.2017.10.046] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/21/2017] [Accepted: 10/28/2017] [Indexed: 12/17/2022]
Abstract
Restoration of extensive bone loss and defects remain as an unfulfilled challenge in modern medicine. Given the critical contributions to bone homeostasis and diseases, mesenchymal stem cells (MSCs) have shown great promise to jumpstart and facilitate bone healing, with immense regenerative potential in both pharmacology-based endogenous MSC rescue/mobilization in skeletal diseases and emerging application of MSC transplantation in bone tissue engineering and cytotherapy. However, efficacy of MSC-based bone regeneration was not always achieved; particularly, fulfillment of MSC-mediated bone healing in diseased microenvironments of host comorbidities remains as a major challenge. Indeed, impacts of diseased microenvironments on MSC function rely not only on the dynamic regulation of resident MSCs by surrounding niche to convoy pathological signals of bone, but also on the profound interplay between transplanted MSCs and recipient components that mediates and modulates therapeutic effects on skeletal conditions. Accordingly, novel solutions have recently been developed, including improving resistance of MSCs to diseased microenvironments, recreating beneficial microenvironments to guarantee MSC-based regeneration, and usage of subcellular vesicles of MSCs in cell-free therapies. In this review, we summarize state-of-the-art knowledge regarding applications and challenges of MSC-mediated bone healing, further offering principles and effective strategies to optimize MSC-based bone regeneration in aging and diseases.
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Affiliation(s)
- Bing-Dong Sui
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Cheng-Hu Hu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China
| | - An-Qi Liu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Chen-Xi Zheng
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Kun Xuan
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Yan Jin
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
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