FASEB bioAdvances最新文献

{"title":"Inhibition of the Hippo pathway by verteporfin reduces the proliferation and stemness of rat hair follicle neural crest stem cells under hypoxia","authors":"Weihai Liu,&nbsp;Suhua Chen,&nbsp;Xin Chen,&nbsp;Lixiang Xue,&nbsp;Yan Wang,&nbsp;Jun Yang","doi":"10.1096/fba.2025-00025","DOIUrl":"https://doi.org/10.1096/fba.2025-00025","url":null,"abstract":"<p>Hair follicle neural crest stem cells reside in the bulge region of the outer root sheath of hair follicles, originate from the ectoderm, and have multidirectional differentiation potential, making them ideal candidates for tissue engineering applications. These cells mainly reside in a hypoxic microenvironment that favors the maintenance of stemness. Recently, many studies have elucidated the involvement of the Hippo pathway in the regulation of stem cell fate. However, few studies have investigated whether the Hippo signaling pathway regulates the growth of hair follicle neural crest stem cells in hypoxic environments. In the present study, we investigated the role of the Hippo pathway in the regulation of hair follicle neural crest stem cells under hypoxic conditions. We identified neural crest-derived stem cells from single-cell RNA-seq data of skin organoids in a public database, and reported that the Hippo pathway was activated in the cell population. Hair follicle neural crest stem cells were isolated from rat hair follicles and cultured under hypoxic (3% oxygen) and normoxic (20% oxygen) conditions. Cell viability was assessed via the CCK8 assay. The expression levels of several key genes, including <i>Hif2α</i>, <i>Nestin</i>, <i>Sox10</i>, <i>Oct4</i>, <i>Nanog</i>, <i>Sox2</i>, and <i>Klf4</i>, were evaluated via quantitative real-time PCR, after which we treated the cells with verteporfin, a small molecule inhibitor of the Hippo pathway. Changes in the subcellular localization of the hair follicle neural crest stem cell-specific marker SOX10 were assessed via immunofluorescence. Western blotting was used to analyze the expression levels of proteins associated with stemness and hypoxia responses, including HIF2α, SOX10, OCT4, NANOG, SOX2, and KLF4. The results showed that hypoxic conditions facilitated the maintenance of stemness in hair follicle neural crest stem cells, including the promotion of proliferation and the expression of multipotential markers. Inhibition of the Hippo pathway results in a significant decrease in cell proliferation. The protein expression of HIF2α, SOX10, OCT4, NANOG, SOX2, and KLF4 was also reduced under hypoxic conditions.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPCR dimerization: Drug discovery aspects and targets in renin-angiotensin systems","authors":"Tahmid Faisal,&nbsp;Tahir Hussain","doi":"10.1096/fba.2024-00180","DOIUrl":"https://doi.org/10.1096/fba.2024-00180","url":null,"abstract":"<p>G protein-coupled receptors (GPCRs), which play crucial roles in various physiological functions, often assembled into dimers and higher-order oligomers. This oligomerization phenomenon has been observed in diverse physiological and pathological contexts, presenting promising opportunities for drug discovery targeting vital systems such as the cardiovascular, nervous, endocrine, and renal systems. This review offers a concise understanding of GPCR dimerization, its signaling mechanisms, and its implications. Furthermore, we explored therapeutic strategies aimed at modulating receptors involved in dimer/oligomer formation within the renin-angiotensin system.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression","authors":"Shalene H. Wilcox,&nbsp;Jouber Calixto,&nbsp;Steven D. Dray,&nbsp;Daniel M. Rasch,&nbsp;Andrew H. Smith,&nbsp;Kole D. Brodowski,&nbsp;Jonathon T. Hill,&nbsp;David M. Thomson","doi":"10.1096/fba.2024-00252","DOIUrl":"https://doi.org/10.1096/fba.2024-00252","url":null,"abstract":"<p>Sarcopenia refers to the decline in muscle mass and function that occurs with advancing age. It is driven by alterations in multiple cellular processes. AMP-activated protein kinase (AMPK) is a cellular energy sensor that opposes many age-related changes, making it an attractive target for the treatment of sarcopenia. This study aimed to test the effect of chronic treatment of old mice with the AMPK-activating prodrug, AICAR, on treadmill running capacity and muscle mass, force production, gene expression, and intracellular markers relevant to sarcopenia. Old (23 months) mice were tested for treadmill running capacity, then randomly assigned to receive daily treatment with AICAR (OA; 300 to 500 mg/kg, delivered via subcutaneous injection) or an equivalent volume of saline vehicle (OS) for 31 days. Young (5 months) saline-treated mice (YS) served as controls. Treadmill posttesting was performed after 24 days, and the mice were euthanized after 31 days of treatment. Extensor digitorum longus (EDL) muscles were tested for force generation and RNA sequencing, RT-PCR, and western blotting were performed on quadricep muscles. Treadmill running capacity declined from pre- to posttesting by 24.5% in OS mice. This decline was not observed in YS or OA mice. Quadricep weight was ~8% higher, and tetanic force production by the EDL muscle increased by 26.4% in OA versus OS. These phenotypic improvements with AICAR treatment were accompanied by changes in gene expression in OA/YS versus OS muscles consistent with the “rejuvenation” of gene ontologies associated with connective tissue, neurodegenerative disease, Akt signaling, and mitochondrial function, among others. AICAR increased the mitochondrial markers cytochrome C by ~33%, and citrate synthase by ~22%. Serum insulin-like growth factor-1 levels increased, and Akt phosphorylation tended (<i>p</i> = 0.07) to increase with AICAR treatment. Although protein levels of the mTORC1 signaling pathway intermediate, rpS6, were higher in OA versus OS muscles, the phosphorylation of mTORC1 pathway intermediates was unaffected. On the other hand, gene expression of the muscle-specific ubiquitin ligases Mafbx and Murf1 were reduced with AICAR treatment. AICAR treatment mildly increased/preserved muscle mass and force production and prevented a decline in treadmill running performance in old mice. These effects were associated with altered skeletal muscle gene and protein expression, suggesting improved mitochondrial content and metabolic signaling (particularly through Akt) as contributing factors to the observed phenotypic effects. Our findings support further development of AMPK-activating drugs as a therapeutic strategy for improving age-related organismal dysfunction and sarcopenia.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium channel-mediated NO-induced vasodilation during maturation: Dominance of Kv7 channels","authors":"Anastasia A. Shvetsova,&nbsp;Dina K. Gaynullina,&nbsp;Peter Winkler,&nbsp;Paulus Wohlfart,&nbsp;Rudolf Schubert","doi":"10.1096/fba.2024-00178","DOIUrl":"https://doi.org/10.1096/fba.2024-00178","url":null,"abstract":"<p>Maturation represents a process characterized by adaptive changes, particularly in the circulatory system. However, it is not known whether, in neonates, potassium channels contribute to NO-induced vasorelaxation at all and, if so, which potassium channels these are. Therefore, this study tested the hypothesis that potassium channels mediate NO-induced vasorelaxation in newborn rats. Young (10- to 15-day-old) and adult (2- to 3-month-old) male rats were studied using real-time PCR, isometric myography, and the sharp microelectrode technique on saphenous arteries. We observed prominent mRNA expression of several distinct isoforms of potassium channel families known to potentially mediate SNP-induced vasodilation. Further, in both adult and young rats, SNP can relax vessels independently of potassium channels. A solely potassium channel-independent anticontractile effect of SNP was observed also when either Kir6, or Kir2, or Kv2 channels, respectively, were available in both adult and young rats. However, when Kv1 channels were available, a Kv1 channel-dependent component contributed to the anticontractile effect of SNP in young rats. When BK_Ca channels were available, a BK_Ca channel-dependent component contributed to the anticontractile effect of SNP in adult rats. A considerable Kv7 channel-dependent component contributed to the anticontractile effect of SNP in both adult and young rats. Thus, the data of the present study show for the first time that potassium channels, even multiple ones, contribute to SNP-induced vasorelaxation in newborn rats and that the potassium channels involved in SNP-induced vasorelaxation change from Kv1/Kv7 channels to BK_Ca/Kv7 channels during postnatal development.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of amylin, a gut–brain axis hormone, in metabolic and neurological disorders","authors":"Tahir Muhammad,&nbsp;Stephen F. Pastore,&nbsp;Katrina Good,&nbsp;Wai Haung Yu,&nbsp;John B. Vincent","doi":"10.1096/fba.2024-00151","DOIUrl":"https://doi.org/10.1096/fba.2024-00151","url":null,"abstract":"<p>Amylin, also known as islet amyloid polypeptide (IAPP), is a pancreatic β<i>-</i>cell peptide hormone involved in satiation and control food intake. It is also produced in smaller quantities by neurons, the gastrointestinal tract, and spinal ganglia. Numerous studies have revealed that patients with type 2 diabetes mellitus (T2DM) and cognitive deficits exhibit IAPP deposits in the pancreas, brain, and blood vessels. IAPP has also been shown to exert neuroprotective effects against Alzheimer's disease (AD) and cognitive impairments. The objective of this review paper is to provide recent information about the pathophysiological roles of IAPP in metabolic and in neurological disorders, and its potential as a druggable target. We have reviewed preclinical and clinical human and animal research studies of IAPP. We discuss the IAPP structure, its receptors, and its physiological functions in metabolism, satiation, adiposity, obesity, and in the brain. Then we discuss its role in metabolic and neurological disorders like diabetes, obesity, bone disorder, neurodegeneration, cerebrovascular disorders, depression, alcohol use disorder, epilepsy, and in ovarian cysts. Overall, this review provides information on the progress of research into the roles of IAPP and its receptor in food intake, energy homeostasis, glucose regulation, satiation, and its role in metabolic and neurological disorders making it a potential target for therapeutic approaches. This review also suggests that the utilization of rodents overexpressing human IAPP in neurodegeneration models may unearth some significant therapeutic potentials for neurological disorders.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of adipose stem cell quality via Cu-MON: Transcriptome and bioinformatics analysis of normal and diabetic stem cells","authors":"Ruixin Pang,&nbsp;Kaijing Liu,&nbsp;Biou Liu,&nbsp;Jing Yang","doi":"10.1096/fba.2024-00153","DOIUrl":"https://doi.org/10.1096/fba.2024-00153","url":null,"abstract":"<p>Transplanted adipose stem cells (ASC) have a low survival rate in the body, and there are not many ASC that can be effectively used, which weakens their tissue repair function. Based on this status quo, a new type of copper-based metal–organic network (Cu-MON) was used to pretreat cells to regulate cell activity in order to improve the efficacy of cell therapy or reduce the number of cells used, thus reducing the cost of clinical treatment. Gene expression changes before and after Cu-MON treatment of normal donor adipose stem cells (ND-ASC) and type 2 diabetes mellitus adipose stem cells (T2DM-ASC) were evaluated through RNA sequencing, KEGG and GO enrichment analysis. The results showed that Cu-MON improved ASC cell quality by regulating immune response and promoting paracrine secretion. IL-17 signaling pathway and IL-6, CXCL8, and MMP-9 were key pathways and necessary genes that affected the ability of stem cells. In addition, Cu-MON also improved stem cell antiviral ability through Type I interferon signaling pathway. Our research showed that Cu-MON had improved the cell quality of ASC by regulating immune response, promoting paracrine secretion, and improving antiviral capabilities. This approach to biomaterial pretreatment is fast, convenient, and relatively safe, and provides new strategies for improving the efficiency of cell therapies.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Nitrodopamine potentiates catecholamine-induced contractions of human isolated vas deferens","authors":"Antonio Tiago Lima,&nbsp;Sami Jabbour,&nbsp;José Britto-Júnior,&nbsp;Demétrio Martinho Ramos de Carvalho,&nbsp;Adriano Fregonesi,&nbsp;Fernanda V. Mariano,&nbsp;Valéria Barbosa de Souza,&nbsp;Andre Almeida Schenka,&nbsp;Edson Antunes,&nbsp;Gilberto De Nucci","doi":"10.1096/fba.2024-00183","DOIUrl":"https://doi.org/10.1096/fba.2024-00183","url":null,"abstract":"<p>6-Nitrodopamine (6-ND) is the main catecholamine released from human isolated vas deferens and the adrenergic nervous system is known to play a major role in the contractions of the epididymal portion of the vas deferens. Here it was investigated the interactions of 6-ND on the contractions of the human isolated vas deferens induced by either classical catecholamines or electric-field stimulation (EFS). The vas deferens obtained from 106 patients who underwent vasectomy surgery were mounted in a 10-mL glass chamber filled with warmed (37°C) and oxygenated Krebs–Henseleit's solution. The strips were pretreated (30 min) with 6-ND (0.1–100 nM) and exposed to increasing concentrations of noradrenaline (0.01–300 M), dopamine (0.00001–10 mM), or adrenaline (0.01–300 M). The strips were also submitted to EFS in tissues pre-incubated or not with 6-ND (1–100 nM), noradrenaline (100 nM), adrenaline (100 nM), or dopamine (100 nM). Catecholamine basal release was evaluated by LC–MS/MS and expression of tyrosine hydroxylase by both immunohistochemistry (IC) and fluorescence in-situ hybridization (FISH). Pre-incubation of the vas deferens with 6-ND caused marked potentiation of the contractions induced by noradrenaline, adrenaline, and dopamine, as characterized by significant increases in E_max, without changes in pEC₅₀ values. 6-nitrodopamine also caused significant increases in the EFS-induced contractions. The basal release of 6-ND was not affected by pre-treatment of the tissues with tetrodotoxin. Tyrosine hydroxylase was detected in epithelial cells of human vas deferens samples by both IC and FISH. The results clearly demonstrate that epithelium-derived 6-ND is a major modulator of human vas deferens contractility.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143252750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The human-specific noncoding RNA RP11-424G14.1 functions at the intersection of sexually dimorphic pathways in inflammation, senescence, and metabolism","authors":"Kameron Kennicott,&nbsp;Yun Liang","doi":"10.1096/fba.2024-00101","DOIUrl":"https://doi.org/10.1096/fba.2024-00101","url":null,"abstract":"<p>Sexual dimorphism is a fundamental characteristic of various physiological and pathological processes in humans, including immune responses, senescence, and metabolism. Most studies on the sex bias have focused on sex hormones or female-biased genes, whereas male-biased genetic factors remain understudied. Here, we show that the Y-linked noncoding RNA, <i>RP11-424G14.1</i>, is expressed in human male keratinocytes. Microarray study suggests the NF-κB pathway as the top biological pathway affected by <i>RP11-424G14.1</i> knockdown, consistent with known sex differences in inflammation. Additionally, <i>IGFBP3</i> is identified as the top gene supported by <i>RP11-424G14.1</i> in male keratinocytes. Conversely, in female keratinocytes, <i>IGFBP3</i> is the top gene repressed by the X-linked long noncoding RNA <i>XIST</i>, suggesting a central role of <i>IGFBP3</i> in mediating sexual dimorphism. Knockdown of <i>RP11-424G14.1</i> or IGFBP3 in male keratinocytes inhibits cellular senescence, consistent with increased longevity in females. IGFBP3 expression is dependent on insulin, and metabolomics analysis suggests that <i>RP11-424G14.1</i> and IGFBP3 regulate acrylcarnitine metabolism. Our study identifies the role of the <i>RP11-424G14.1-</i>IGFBP3 pathway in coordinating sex differences in immunity, senescence, and metabolism. With <i>RP11-424G14.1</i> being a human-specific genetic element, our study suggests the evolving feature of sexual dimorphisms in biological processes.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143249041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCAPD3-mediated AKT activation regulates prostate cancer progression","authors":"Yi Zhang,&nbsp;Wanlin Xie,&nbsp;Xicui Zong,&nbsp;Yuanyuan Fang,&nbsp;Jia Ren,&nbsp;Zuolei Jing,&nbsp;Yong Wei,&nbsp;Shan Lu,&nbsp;Qingyi Zhu,&nbsp;Ping Liu","doi":"10.1096/fba.2024-00073","DOIUrl":"https://doi.org/10.1096/fba.2024-00073","url":null,"abstract":"<p>Despite therapeutic improvements in prostate cancer treatment, the recurrence and mortality rates are still high, and the underlying mechanisms still need further study. Non-SMC Condensin II Complex Subunit D3 (NCAPD3) is a subunit of condensin II complex, mainly involved in the mitotic chromosome condensation of cells. This study aimed to figure out the detailed mechanisms by which NCAPD3 contributed to prostate cancer development. Clinical samples and cell lines were used to measure the expression of genes by quantitative real-time RT-PCR (qRT-PCR), Western-blot assay (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and dual-luciferase reporter assays were examined to explore the interplays between molecules. CCK8, transwell, and wound-healing assays were applied to perform cell proliferation and migration. A subcutaneous tumor xenograft model was constructed by injecting DU145-Lv-NCAPD3 cells and control cells into male BALB/c nude mice to confirm the result derived from in vitro assay. NCAPD3 increased STAT3 expression and phosphorylation in PCa cells, thereby enhancing STAT3 transcriptional activity to improve the levels of JAK2 and EZH2. This led to an increase in phosphorylation of AKT at Thr 308 and Ser 473 through JAK2/PI3K and EZH2/NSD2/mTORC2 pathways, respectively. Moreover, there was a positive mutual activation between STAT3 and JAK2, further enhanced by NCAPD3 to promote PCa progression. NCAPD3, as an oncogene, promoted PCa progression by phosphorylating and activating AKT, which suggests a novel functional pathway of NCAPD3 in promoting PCa progression.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cementum attachment protein-derived peptide induces cementum formation","authors":"Lía Hoz Rodríguez,&nbsp;Maricela Santana Vázquez,&nbsp;Luis Fernando Ramírez González,&nbsp;Gonzalo Montoya Ayala,&nbsp;Sonia López Letayf,&nbsp;A. Sampath Narayanan,&nbsp;Higinio Arzate","doi":"10.1096/fba.2024-00119","DOIUrl":"https://doi.org/10.1096/fba.2024-00119","url":null,"abstract":"<p>A pentapeptide AVIFM (CAP-p5) derived from the carboxy-terminus end of cementum attachment protein was examined for its role on proliferation, differentiation, and mineralization of human periodontal ligament cells (HPLC), and for its potential to induce cementum deposition in vivo. CAP-p5 capability to induce hydroxyapatite crystal formation on demineralized dentin blocks was characterized by scanning electron microscopy, μRAMAN, and high-resolution transmission electron microscopy. The results revealed that CAP-p5 promoted cell proliferation and cell differentiation and increases alkaline phosphatase activity of HPLC and mineralization at an optimal concentration of 10 μg/mL. It induced the expression of cementum molecular markers BSP, CAP, CEMP1, and ALP at the protein level. In a cell-free system, human demineralized dentin blocks coated with CAP-p5 induced the deposition of a homogeneous and continuous mineralized layer, intimately integrated with the underlying dentin indicating new cementum formation. Physicochemical characterization of this mineral layer showed that it is composed of hydroxyapatite crystals. Demineralized dentin blocks coated with CAP-p5 implanted subcutaneously in BALB/cAnNCrl were analyzed histologically; the results disclosed that CAP-p5 could induce the deposition of a cementum layer intimately integrated with the subjacent dentin with cementocytes embedded into the cementum matrix. Immunostaining showed the expression of cementum molecular markers; <i>v.gr.</i> BSP, CAP, CEMP1 and ALP, validating the molecular identity of the newly deposited cementum. We conclude that CAP-p5 is a new biomolecule with the potential of therapeutic application to contribute to the regeneration of cementum and periodontal structures lost in periodontal disease.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}