Paulo Cerri | Universidade Estadual Paulista "Júlio de Mesquita Filho" (original) (raw)

Papers by Paulo Cerri

Molecular Biology of the Cell, 2013

Developmental Biology, Oct 1, 2021

Vascular endothelial growth factor A (VEGF-A) is expressed by several cell types and is a crucial... more Vascular endothelial growth factor A (VEGF-A) is expressed by several cell types and is a crucial factor for angiogenic-osteogenic coupling. However, the immunolocalization of VEGF-A during the early stages of the alveolar process formation remains underexplored. Thus, we analyzed the spatio-temporal immunolocalization of VEGF-A and its relationship with Runt-related transcription factor 2 (Runx2) and osterix (Osx) during the early steps of intramembranous ossification of the alveolar process in rat embryos. Embryo heads (E) of 16, 18 and 20-day-old rats were processed for paraffin embedding. Histomorphometry and immunohistochemistry to detect VEGF-A, Runx2, and Osx (osteoblast differentiation markers) were performed. The volume density of bone tissue including bone cells and blood vessels increased significantly in E18 and E20. Cells showing high VEGF-A immunoreactivity were initially observed within a perivascular niche in the ectomesenchyme; afterwards, these cells were diffusely located near bone formation sites. Runx2-and Osx-immunopositive cells were observed in corresponded regions of cells showing strong VEGF-A immunoreactivity. Although these immunostained cells were observed in all specimens, this immunolocalization pattern was more evident in E16 specimens and gradually decreased in E18 and E20 specimens. Double immunofluorescence labelling showed intracellular co-localization of Osx and VEGF-A in cells surrounding the developing alveolar process, indicating a crucial role of VEGF-A in osteoblast differentiation. Our results showed VEGF-A immunoexpression in osteoblasts and its precursors during the maxillary alveolar process formation of rat embryos. Moreover, the VEGF-A-positive cells located within a perivascular niche at the early stages of the alveolar process development suggest a crosstalk between endothelium and ectomesenchymal cells, reinforcing the angiogenic-osteogenic coupling in this process.

Clinical Oral Investigations, Apr 4, 2023

Life Sciences, Feb 1, 2023

International Endodontic Journal, Nov 22, 2022

AimTo evaluate whether the bioceramic materials Bio‐C Pulpo (Bio‐C, Angelus) and mineral trioxide... more AimTo evaluate whether the bioceramic materials Bio‐C Pulpo (Bio‐C, Angelus) and mineral trioxide aggregate (MTA) Repair HP (MTA‐HP, Angelus) induce fibroblast proliferation and release of interleukin‐10 (IL‐10), an anti‐inflammatory cytokine, stimulating connective tissue remodelling. The tissue response of Bio‐C and MTA‐HP was compared with the White MTA (WMTA; Angelus) since studies have demonstrated that WMTA induces tissue repair.MethodologyBio‐C, MTA‐HP and WMTA were inserted into polyethylene tubes and implanted in the subcutaneous tissue of Holtzman rats for 7, 15, 30 and 60 days. As a control group (CG), empty tubes were implanted subcutaneously. The number of fibroblasts (FB), Ki‐67‐, fibroblast growth factor‐1‐ (FGF‐1) and IL‐10‐immunolabelled cells and collagen content in the capsules was obtained. The data were subjected to two‐way anova followed by Tukey's test (p ≤ .05).ResultsAt 7 days, significant differences in the number of FB were not detected amongst Bio‐C, MTA‐HP and WMTA groups (p ˃ .05). The capsules of all groups exhibited a significant increase in the number of FB and content of collagen over time. From 7 to 60 days, a significant reduction in the number of FGF‐1‐ and Ki‐67‐immunolabelled cells was seen in the capsules of all specimens. In all periods, no significant difference in the number of FGF‐1‐immunolabelled cells was detected between Bio‐C and CG specimens. At 60 days, significant differences in the immunoexpression of FGF‐1 were not observed amongst the groups. At 7 and 15 days, the highest immunoexpression for Ki‐67 was present in Bio‐C specimens whilst, after 30 and 60 days, no significant difference was observed amongst the bioceramic materials. At 7 days, few IL‐10 immunolabelled cells were present in the capsules of all specimens whereas, at 60 days, a significant increase in the IL‐10‐immunostaining was present in all groups. At 60 days, the Bio‐C, MTA‐HP and WMTA groups showed a greater number of IL‐10‐immunolabelled cells than in the CG specimens (p < .0001).ConclusionsBio‐C, MTA‐HP and WMTA stimulate fibroblast proliferation, leading to the formation of collagen‐rich capsules. FGF‐1 and IL‐10 may mediate the remodelling of capsules around Bio‐C, MTA‐HP and WMTA bioceramic materials.

Biomedical Physics & Engineering Express, Nov 25, 2022

Several synthetic and natural materials have been studied for the confection of temporary grafts ... more Several synthetic and natural materials have been studied for the confection of temporary grafts for application in regenerative medicine, however, the development of a material with adequate properties remains a challenge, mainly because its degradation kinetics in biological systems. Nature provides materials with noble properties that can be used as such for many applications, thus, taking advantage of the available morphology and assembled structures of plants, we propose to study the vegetable stems for use as temporary graft. Since the in vivo degradation is maybe one of the most important features of the temporary grafts, here we have implanted the plant stems from pumpkin, papaya, and castor into the subepithelial tissue of animals and followed their biodegradation process and the local inflammatory response. Mechanical tests, FTIR and contact angle with water were also analysed. The results indicated the mechanical properties and the contact angle were adequate for use in regenerative medicine. The results of the in vivo studies indicated a beneficial inflammatory process and a gradual disintegration of the materials within 60 days, suggesting the plants stems as new and potential materials for development of grafts for use in the field of regenerative medicine.

Reproduction, Jun 1, 2018

The cauda epididymidis is the major sperm storage region whose androgenic supply, essential for t... more The cauda epididymidis is the major sperm storage region whose androgenic supply, essential for the sperm viability, is provided by the vasculature and is dependent upon testosterone diffusion through the stromal tissue to reach the epithelial cells. We have focused our efforts on examining the regulation of this important epididymal region by evaluating the impact of the androgen disrupter cimetidine on the epithelial-stromal androgenic microenvironment. Male rats received 100 mg/kg cimetidine (CMTG) or saline (CG) for 50 days, serum testosterone levels were measured and the epididymal cauda region was processed for light and transmission electron microscopy. In the proximal cauda region, the duct diameter was measured and birefringent collagen in the stroma was quantified. TUNEL-labeled epithelial cells were quantified, and androgen receptor (AR), karyopherin alpha (KPNA) and sex hormonebinding globulin (SHBG) levels were analyzed by immunofluorescence and Western blot. CMTG showed reduced duct diameter and high number of apoptotic epithelial cells. In the epithelium, the total AR concentration and the KPNA immunoreactivity were reduced, and a weak/absent AR nuclear immunofluorescence was observed in contrast to the enhanced AR immunolabeling observed in the cytoplasm of the epithelial cells. A significant reduction of collagen and SHBG levels in the stroma was also observed. Cimetidine treatment impairs AR nuclear import in the epithelium, causing androgenic dysfunction and subsequent epithelial cell apoptosis and duct atrophy. The connective tissue atrophy and reduction of SHBG stromal levels associated with epithelial androgenic dysfunction indicate a possible role of stromal SHBG in the androgenic supply of the sperm storage region of the epididymis.

International Endodontic Journal, Sep 27, 2020

International Endodontic Journal, Feb 1, 2016

Aim To evaluate the inflammatory process induced by Biodentine and mineral trioxide aggregate (MT... more Aim To evaluate the inflammatory process induced by Biodentine and mineral trioxide aggregate (MTA) in rat subcutaneous tissues. Methodology A polyethylene tube filled with Biodentine (n = 20) or MTA (n = 20) was placed into the dorsal subcutaneous of forty male rats; in the control group (CG; n = 20), empty tubes were implanted. After 7, 15, 30 and 60 days, the polyethylene tubes surrounded by connective tissue were fixed and embedded in paraffin. The number of inflammatory cells was estimated in HE-stained sections; numerical density of interleukin-6 (IL-6)-immunolabelled cells was also performed. The differences amongst the groups were analysed statistically by Tukey's test (P ≤ 0.05). Results A high number of inflammatory cells and IL-6-positive cells were observed at 7 days, in all groups; however, in the Biodentine group, the number of inflammatory cells and IL-6-immunolabelled cells was significantly higher (P ≤ 0.05) in comparison with the other groups at 7 and 15 days. In the capsules of animals from all groups, a gradual and significant reduction (P ≤ 0.05) of these parameters was seen over time. At 60 days, the capsules exhibited numerous fibroblasts and bundles of collagen fibres; in addition, the number of IL-6-positive cells was not significantly different amongst Biodentine, MTA and control groups. Conclusions There was a significant regression in the inflammatory reaction in the capsules indicating, therefore, that Biodentine is a biocompatible material.

Molecular Biology of the Cell, 2015

Life Sciences, 2022

Venlafaxine, a norepinephrine and serotonin reuptake inhibitor, impairs rat sperm parameters, spe... more Venlafaxine, a norepinephrine and serotonin reuptake inhibitor, impairs rat sperm parameters, spermatogenesis and causes high intratesticular estrogen and testosterone levels, indicating that Leydig cells (LCs) may be a venlafaxine target. We evaluated the effect of venlafaxine treatment on LCs in vivo, focusing on adrenergic signaling, EGF immunoexpression and steroidogenesis. Germ cells mitotic/meiotic activity and UCHL1 levels were also evaluated in the seminiferous epithelium. Adult male rats received venlafaxine (30 mg/kg) or distilled water. In testicular sections, the seminiferous tubules, epithelium and the LCs nuclear areas were measured, and the immunoexpression of Ki-67, UCHL1, StAR, EGF, c-Kit and 17β-HSD was evaluated. UCHL1, StAR and EGF protein levels and Adra1a, Nur77 and Ndrg2 expression were analyzed. MDA and nitrite testicular levels, and serum estrogen and testosterone levels were measured. Venlafaxine induced LCs hypertrophy and Ndrg2 upregulation, in parallel to increased number of Ki-67, c-Kit- and 17β-HSD-positive interstitial cells, indicating that this antidepressant stimulates LCs lineage proliferation and differentiation. Upregulation of Adra1a and Nur77 could explain the high levels of StAR and testosterone levels, as well as aromatization. Enhanced EGF immunoexpresion in LCs suggests that this growth fact is involved in adrenergically-induced steroidogenesis, likely via upregulation of Nur77. Slight tubular atrophy and weak Ki-67 immunoexpression in germ cells, in association with high UCHL1 levels, indicate that spermatogenesis is likely impaired by this enzyme under supraphysiological estrogen levels. These data corroborate the unchanged MDA and nitrite levels. Therefore, venlafaxine stimulates LCs steroidogenesis via adrenergic signaling, and EGF may be involved in this process.

Archives of Oral Biology, Oct 1, 2021

OBJECTIVES The present study aimed to compare two different models of orthodontic tooth movement ... more OBJECTIVES The present study aimed to compare two different models of orthodontic tooth movement (OTM) in rats by evaluating tooth movement efficiency and periodontal tissues remodelling. DESIGN Fifteen animals were randomly distributed into 3 groups: control group (untreated); ligature appliance (LA) as experimental OTM using a closed coil spring fixed around maxillary first molar by steel ligature; occlusal appliance (OA) as experimental OTM using a closed coil spring attached on the occlusal surface of the maxillary first molar. After 15 days, all animals were euthanized, and the maxilla of each animal was collected for qPCR, micro-computed tomography, and histological analyses. RESULTS Interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha gene expressions were significantly upregulated in the animals of the LA group as compared to the other groups. No significant difference was observed in tooth displacement between both methods. The LA group presented higher linear bone loss and lower values of bone volume fraction, bone mineral density, trabecular number and increased values of trabecular separation compared to the other groups. The birefringent collagen content in the tension side of the periodontal ligament contained significantly lower collagen content in the LA group than in the control group. Furthermore, on the pressure side, the collagen content was significantly lower in the LA and OA groups than in the control group. CONCLUSIONS The OA group presented little or no deleterious effect on periodontal tissues compared to the LA group, suggesting its use may be more reliable for OTM induction in rats for 15 days.

International Endodontic Journal, Jul 12, 2021

AimTo evaluate the tissue response promoted by Bio‐C Pulpo (Bio), MTA Repair HP (MTA‐HP) and Whit... more AimTo evaluate the tissue response promoted by Bio‐C Pulpo (Bio), MTA Repair HP (MTA‐HP) and White MTA (WMTA) and whether these materials cause liver changes in a rat experimental model.MethodologyPolyethylene tubes filled with Bio, MTA‐HP and WMTA, and empty tubes (control group, CG) were implanted into the subcutaneous tissues of rats for 7, 15, 30 and 60 days. Inflammatory reaction score (IRS), capsule thickness, number of inflammatory cells (IC), von Kossa reaction, interleukin‐6 (IL‐6) and alkaline phosphatase (ALP) immunohistochemistry reactions were performed. Combined methods, von Kossa followed by immunohistochemistry for detection of ALP, were performed. At 60 days, the serum glutamic‐oxaloacetic transaminase (GOT) and glutamic‐pyruvic transaminase (GPT) levels were measured and liver fragments were collected for histological analysis; the data were assessed by one‐way ANOVA analysis followed by Sidak's post‐test. The biocompatibility and bioactivity data were subjected to the two‐way ANOVA analysis followed by Tukey post hoc test, except the IRS. The IRS data were subjected to the Kruskal–Wallis ANOVA non‐parametric test followed by Dunn's test (p ≤ .05).ResultsNo significant difference was detected in serum GOT and GPT concentrations and in the number of hepatocytes among the experimental and CG samples. Although Bio‐C Pulpo had the highest IC and IL‐6‐immunolabelled cells (p < 0.0001) at all periods, no significant difference was observed in the IRS among the materials, except at 60 days. In this period, the WMTA had lower IRS. All groups had a significant reduction in the capsule thickness and in the number of IC and IL‐6‐immunolabelled cells over time. Bio‐C Pulpo, MTA‐HP and WMTA specimens had greater immunoexpression of ALP than CG (p < .0001). At all periods, von Kossa‐positive and birefringent structures were observed in the capsules around the materials. ALP‐immunolabelled cells were also seen near von Kossa‐positive structures.ConclusionsBio‐C Pulpo, MTA‐HP and WMTA materials did not cause morphological changes in the liver and no significant alteration in the serum GOT and GPT levels. Moreover, these bioceramic materials were biocompatible and exhibited bioactive potential. However, Bio‐C Pulpo induced greater inflammatory infiltrate than MTA‐HP and WMTA at all periods.

Journal of Endodontics, Oct 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

International Endodontic Journal, Oct 12, 2010

Aim To evaluate the biological response of the periodontium adjacent to furcation perforations in... more Aim To evaluate the biological response of the periodontium adjacent to furcation perforations in rat molars filled with Endo-CPM-Sealer (CPM), MTA-Angelus (MTA) or zinc oxide-eugenol cement (ZOE). Methodology The pulp chamber floors of maxillary right first molar teeth were perforated and sealed with CPM, mineral trioxide aggregate (MTA) or ZOE; the left first molars, without any treatment, were used as controls (CG). After 7, 15, 30 and 60 days, fragments of maxilla were fixed, decalcified and embedded in paraffin. Sections were stained with H&E, Masson's trichrome and submitted to tartrate-resistant acid phosphatase (TRAP) reaction, used as an osteoclast marker. The width of the periodontal space, the numerical density of inflammatory cells and the number of TRAP-positive osteoclasts in the bone surface were measured, and statistical analyses were performed using analysis of variance and Tukey test (P £ 0.05). Results In all experimental groups, the greatest number of inflammatory cells was observed at 7 days, especially in the ZOE group. In this group, the intense inflammatory process was related to a significant increase (P £ 0.05) in the number of osteoclasts and, thereby, in an increase in the width of the periodontal space. At 60 days, no significant differences in osteoclast numbers amongst CPM, MTA and CG groups occurred; the periodontal space was also significantly reduced in the experimental groups in comparison with the initial periods. However, in the ZOE group, the periodontal space was significantly larger (P £ 0.05) in comparison with MTA-based materials. Conclusions The periodontium adjacent to perforations filled with MTA and CPM exhibited clear evidence of re-establishment and thus better biocompatibility than ZOE.

Journal of Anatomy, Nov 17, 2009

The role of estrogen in bone resorption has been specifically related to the effect of estrogen o... more The role of estrogen in bone resorption has been specifically related to the effect of estrogen on the signalling pathway that inhibits the formation of osteoclasts. However, osteoclast apoptosis and a significant reduction in the number of these cells have been observed in the alveolar bone of female rats treated with estradiol. In the present study, the expression of estrogen receptor β (ERβ) in the cells of alveolar bone was evaluated in estradiol-treated and -untreated female rats. In order to test the possible direct action of estrogen on osteoclasts, the relationship between apoptosis and ERβ expression in these cells was also analysed. The animals received estradiol for 14 days and the alveolar bone fragments were embedded in paraffin for the quantification of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of ERβ and apoptosis in the osteoclasts were evaluated by ERβ immunohistochemistry and Terminal deoxynucleotidyl transferase-mediated dUTP Nick-End Labelling (TUNEL) methods, respectively. To confirm osteoclast death by apoptosis, these cells were analysed under transmission electron microscopy. Some osteoclasts from estradiol-treated animals were found to be undergoing apoptosis and the number of tartrate-resistant acid phosphatase-positive osteoclasts was significantly reduced. ERβ immunolabelling was observed in the cytoplasm and nuclei of active osteoblasts, osteocytes and osteoclasts in both groups, suggesting a direct participation of estrogen on alveolar bone cells. However, following estradiol treatment, a strong ERβ immunolabelling was often observed in the TUNEL-positive osteoclasts. Therefore, these results indicate that, in addition to the other signalling pathway, the reduction of alveolar bone resorption is also related to a direct action of estrogen on osteoclasts, promoting apoptosis in these cells, via ERβ.

Fertility and Sterility, Sep 1, 2019

International Journal of Andrology, Sep 9, 2020

Venlafaxine (selective serotonin and norepinephrine reuptake inhibitor) use has increased worldwi... more Venlafaxine (selective serotonin and norepinephrine reuptake inhibitor) use has increased worldwide. However, the impact of venlafaxine on testes and sperm parameters has not been investigated.

Histochemistry and Cell Biology, Sep 13, 2021

The role of cytokines in testicular function under normal conditions has not been completely unde... more The role of cytokines in testicular function under normal conditions has not been completely understood. Here, we evaluated testicular macrophages (TM), steroidogenesis by Leydig cells (LC) and seminiferous tubules integrity in cytokines-deficient rat testes induced by diacerein, an anti-inflammatory drug that inhibits interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). Male rats received daily 100 mg/kg of diacerein (DIAG; n = 8) or saline (CG; n = 8) for 30 days. Serum testosterone (T) levels were measured and the seminiferous tubule (ST) area, epithelial area (EA), frequency of damaged ST and number of Sertoli cells (SC) were evaluated. TUNEL method and immunoreactions for detection of pro-IL-1β, TNF-α, steroidogenic acute regulatory protein (StAR), 17β-hydroxysteroid dehydrogenase (17β-HSD), androgen receptor (AR) and scavenger receptor for hemoglobin-haptoglobin complexes (CD163), a TM marker, were performed. Testicular AR, 17β-HSD and IL-1β levels were detected by Western blot. Data were submitted to Student t test (p ≤ 0.05). In DIAG, T and testicular AR, 17β-HSD and IL-1β levels decreased significantly (p < 0.05). The number of TUNEL-positive interstitial cells increased and LC showed weak StAR, 17β-HSD and AR immunoexpression in association with reduced IL-1β immunoexpression and number of CD163positive TM in the interstitial tissue from diacerein-treated rats. Numerous damaged ST were found in DIAG, and reduction in the EA were associated with germ cells death. Moreover, the number of SC reduced and weak AR and TNF-α immunoexpression was observed in SC and germ cells, respectively. The cytokines deficiency induced by diacerein impairs TM, LC and spermatogenesis, and points to a role of IL-1β in steroidogenesis under normal conditions. In the ST, the weak AR and TNF-α immunoexpression in SC and germ cells, respectively, reinforces the idea that TNF-α plays a role in the SC androgenic control.

International Endodontic Journal, Aug 17, 2018

Introduction: The aim of this study was to evaluate the biocompatibility of mineral trioxide aggr... more Introduction: The aim of this study was to evaluate the biocompatibility of mineral trioxide aggregate mixed with selective hydration accelerators such as calcium chloride (CaCl 2), citric acid (CA), and calcium lactate gluconate solution (CLG). Methods: Inductively coupled plasma-atomic emission spectrometry analysis was used to measure calcium ions in the extracts of test materials. The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide assay was performed using MG-63 cells to examine the cytotoxicity of the test materials. The surface of each sample and the growth pattern of the attached cells were observed using scanning electron microscopy (SEM). Results: MTA mixed with 10 wt% CaCl 2 and MTA mixed with 43.4 wt% CLG released a higher amount of calcium ions than the other groups. The 2,3bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide assay revealed that the cell viability of MTA mixed with 0.1 wt% CA was significantly higher than pure MTA on 7-day extract (P < .05). MTA mixed with 43.4 wt% CLG showed significantly higher cell viability than the other groups on 1-day extract (P < .05). MTA mixed with 10 wt% CaCl 2 in all groups showed the lowest cell viability at all time points (P < .05). Under SEM, elongated and confluent cells were observed in all samples except in samples of MTA mixed with 10 wt% CaCl 2. Conclusions: MTA mixed with 0.1 wt% CA showed good biocompatibility. MTA mixed with 43.4 wt% CLG showed favorable biocompatibility on 1 day. MTA mixed with 10 wt% CaCl 2 in all groups showed the lowest cell viability at every time point and poor cell attachment under SEM.