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Journal of Functional Biomaterials Jun 2024Over the last decades, a variety of biomaterials, ranging from synthetic products to autologous and heterologous grafts, have been recommended to conserve and regenerate...
Over the last decades, a variety of biomaterials, ranging from synthetic products to autologous and heterologous grafts, have been recommended to conserve and regenerate bone tissue after tooth extraction. We conducted a biochemical study on ground extracted teeth that aimed to evaluate the osteoinductive and osteoconductive potential of dentin by assessing the releases of bone morphogenetic protein (BMP-2), osteocalcin (OC) and osteonectin (ON) over time (24 h, 10 days and 28 days). Twenty-six patients, who required the extraction of nonrestorable teeth, were enrolled in the study according to the inclusion criteria, as follows: thirteen young patients 18 to 49 years of age (UNDER 50), and thirteen patients of 50 to 70 years (OVER 50); a total of twenty-six teeth were extracted, ground and analyzed by enzyme-linked immunosorbent assays (ELISA). All ground teeth released BMP-2, OC and ON at each time point; no differences were observed between the UNDER-50 and OVER-50 patients. The results of the study support the use of autologous dentin as osteoinductive material for bone regeneration procedures, irrespective of patients' ages.
PubMed: 38921535
DOI: 10.3390/jfb15060162 -
Experimental Dermatology Jun 2024Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth....
Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that SPOCK2 plays important roles in the progression of various human cancers; however, the role of SPOCK2 in melanoma remains unknown. Therefore, this study investigated the roles of SPOCK2 and the related mechanisms in melanoma progression. To evaluate the clinical significance of SPOCK2 expression in patients with melanoma, we analysed the association between SPOCK2 expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of Spock2 in melanoma progression in vitro and in vivo, we knocked down Spock2 in the B16F10 melanoma cell line. High SPOCK2 levels were positively associated with good prognosis and long survival rate of patients with melanoma. Spock2 knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, Spock2 downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in Spock2 knockdown cells. Therefore, Spock2 could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, Spock2 knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that SPOCK2 plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.
Topics: Animals; Female; Humans; Male; Mice; Apoptosis; Biomarkers, Tumor; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Gene Knockdown Techniques; MAP Kinase Signaling System; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2; Melanoma; Melanoma, Experimental; Mice, Inbred C57BL; Neoplasm Invasiveness; Prognosis; Proteoglycans; Skin Neoplasms
PubMed: 38888196
DOI: 10.1111/exd.15092 -
Experimental Oncology May 2024Breast cancer (BCa) is one of the most common oncological diseases in women in Ukraine and worldwide, which determines the need to search for new diagnostic and...
BACKGROUND
Breast cancer (BCa) is one of the most common oncological diseases in women in Ukraine and worldwide, which determines the need to search for new diagnostic and prognostic markers. In this aspect, the study of multicellular proteins, in particular osteopontin (OPN) and osteonectin (ON), in BCа tissue is relevant. The aim of the work was to investigate the expression of SPP1 and SPARC at the mRNA and protein levels in BCa tissue and to assess their relationship with the main clinicopathological BCa characteristics and the survival rates of patients.
MATERIALS AND METHODS
The work was based on the analysis of the results of the examination and treatment of 60 patients with stage II-III BCa and 15 patients with breast fibroadenomas. SPP1 and SPARC mRNA levels were determined by real-time PCR. The study of the expression of protein products of the SPP1 and SPARC genes was carried out by the immunohistochemical method.
RESULTS
We have established that the BCa tissue was characterized by 3.5 (p < 0.05) and 7.4 (p < 0.05) lower levels of SPP1 and SPARC mRNA, respectively, compared to the tissue of benign neoplasms, while OPN and ON expression levels were 1.6 (p < 0.05) and 5.6 (p < 0.05) times higher, respectively, compared to fibroadenoma tissue. The analysis of the relationship between the expression of SPP1 and SPARC at the protein and mRNA levels in BCa tissue and the main clinicopathological BCa characteristics revealed its dependence on the presence of metastases in regional lymph nodes, differentiation grade, and the molecular BCa subtype. Also, high expression levels of SPP1 and OPN were associated with worse patient survival rates.
CONCLUSION
The obtained results indicate the perspective of using SPP1 and SPARC expression indices in BCa tissue to assess the aggressiveness of the cancer course and optimize the tactics of treating patients.
Topics: Humans; Osteonectin; Osteopontin; Female; Breast Neoplasms; Middle Aged; Adult; Aged; Prognosis; Biomarkers, Tumor; Neoplasm Staging; RNA, Messenger; Gene Expression Regulation, Neoplastic
PubMed: 38852057
DOI: 10.15407/exp-oncology.2024.01.013 -
International Dental Journal Apr 2024The present study aimed to (1) investigate biocompatibility and cytotoxicity of pulp-capping materials on viability of human dental pulp stem cells (hDPSCs); (2)...
OBJECTIVES
The present study aimed to (1) investigate biocompatibility and cytotoxicity of pulp-capping materials on viability of human dental pulp stem cells (hDPSCs); (2) determine angiogenic, odontogenic, and osteogenic marker mRNA expressions; and (3) observe changes in surface morphology of the hDPSCs using scanning electron microscopy (SEM).
METHODS
Impacted third molars were used to isolate the hDPSCs, which were treated with extract-release fluids of the pulp-capping materials (Harvard BioCal-Cap, NeoPUTTY MTA, TheraCal LC, and Dycal). Effects of the capping materials on cell viability were assessed using 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay and the apoptotic/necrotic cell ratios and reactive oxygen species (ROS) levels from flow cytometry. Marker expressions (alkaline phosphatase [ALP], osteocalcin [OCN], collagen type I alpha 1 [Col1A], secreted protein acidic and rich in cysteine [SPARC], osteonectin [ON], and vascular endothelial growth factor [VEGF]) were determined by quantitative reverse-transcription polymerase chain reaction. Changes in surface morphology of the hDPSCs were visualised by SEM.
RESULTS
The MTS assay results at days 1, 3, 5, and 7 indicated that Harvard BioCal-Cap, NeoPUTTY MTA, and TheraCal LC did not adversely affect cell viability when compared with the control group. According to the MTS assay results at day 14, no significant difference was found amongst Dycal, Harvard BioCal-Cap, NeoPUTTY MTA, and TheraCal LC affecting cell viability. Dycal was the only capping material that increased ROS level. High levels of VEGF expression were observed with Harvard BioCal-Cap, TheraCal LC, and NeoPUTTY MTA. NeoPUTTY MTA, and Dycal upregulated OCN expression, whereas TheraCal LC upregulated Col1A and SPARC expression. Only Dycal increased ALP expression. HDSCs were visualized in characteristic spindle morphology on SEM when treated with TheraCal LC and Harvard BioCal-Cap.
CONCLUSIONS
NeoPUTTY MTA and Harvard BioCal-Cap showed suitable biocompatibility values; in particular, these pulp-capping materials were observed to support the angiogenic marker.
PubMed: 38692961
DOI: 10.1016/j.identj.2024.04.006 -
FASEB Journal : Official Publication of... Apr 2024Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal...
Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.
Topics: Animals; Mice; Asymmetric Cell Division; Cell Differentiation; MAP Kinase Signaling System; Osteonectin; Signal Transduction
PubMed: 38597911
DOI: 10.1096/fj.202302614R -
Journal of Cranio-maxillo-facial... Jun 2024Axial vascularization of tissue constructs is essential to maintain an adequate blood supply for a stable regeneration of a clinically relevant tissue size. The...
Axial vascularization of tissue constructs is essential to maintain an adequate blood supply for a stable regeneration of a clinically relevant tissue size. The versatility of the arterio-venous loop (AVL) has been previously shown in various small and large animal models as well as in clinical reports for bone regeneration. We have previously demonstrated the capability of the AVL to induce axial vascularization and to support the nourishment of tissue constructs in small animal models after applying high doses of ionizing radiation comparable to those applied for adjuvant radiotherapy after head and neck cancer. We hypothesize that this robust ability to induce regeneration after irradiation could be related to a state of hypoxia inside the constructs that triggers the HIF1 (hypoxia induced factor 1) - SDF1 (stromal derived factor 1) axis leading to chemotaxis of progenitor cells and induction of tissue regeneration and vascularization. We analyzed the expression of HIF1 and SDF1 via immunofluorescence in axially vascularized bone tissue engineering constructs in Lewis rats 2 and 5 weeks after local irradiation with 9Gy or 15Gy. We also analyzed the expression of various genes for osteogenic differentiation (collagen 1, RUNX, alkaline phosphatase and osteonectin) via real time PCR analysis. The expression of HIF1 and SDF1 was enhanced two weeks after irradiation with 15Gy in comparison to non-irradiated constructs. The expression of osteogenic markers was enhanced at the 5-weeks time point with significant results regarding collagen, alkaline phosphatase and osteonectin. These results indicate that the hypoxia within the AVL constructs together with an enhanced SDF1 expression probably play a role in promoting tissue differentiation. The process of tissue generation triggered by hypoxia in the vicinity of a definite vascular axis with enhanced tissue differentiation over time resembles hereby the well-known concept of organogenesis in fetal life.
Topics: Tissue Engineering; Animals; Rats; Chemokine CXCL12; Organogenesis; Neovascularization, Physiologic; Osteogenesis; Hypoxia; Bone Regeneration; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor 1
PubMed: 38582676
DOI: 10.1016/j.jcms.2024.03.020 -
Biochemical Pharmacology May 2024The enzyme tryptophan 2,3-dioxygenase (TDO2) has been implicated in the dysregulation across a variety of human cancers. Despite this association, the implications of...
The enzyme tryptophan 2,3-dioxygenase (TDO2) has been implicated in the dysregulation across a variety of human cancers. Despite this association, the implications of TDO2 in the progression of bladder cancer have eluded thorough understanding. In this study, we demonstrate that TDO2 expression is notably elevated in bladder cancer tissues and serves as an unfavorable prognostic factor for overall survival. Through a series of biological functional assays, we have determined that TDO2 essentially enhances cell proliferation, metastatic potential, and imparts a decreased sensitivity to the chemotherapeutic agent cisplatin. Our mechanistic investigations reveal that TDO2 augments aryl hydrocarbon receptor (AhR) signaling pathways and subsequently upregulates the expression of SPARC and FILIP1L. Importantly, we have identified a positive correlation between TDO2 levels and the basal/squamous subtype of bladder cancer, and we provide evidence to suggest that TDO2 expression is modulated by the tumor suppressors RB1 and TP53. From a therapeutic perspective, we demonstrate that the targeted inhibition of TDO2 with the molecular inhibitor 680C91 markedly attenuates tumor growth and metastasis while concurrently enhancing the efficacy of cisplatin. These findings open a new therapeutic avenue for the management of bladder cancer.
Topics: Humans; Tryptophan Oxygenase; Cisplatin; Receptors, Aryl Hydrocarbon; Tryptophan; Urinary Bladder Neoplasms; Intracellular Signaling Peptides and Proteins; Osteonectin
PubMed: 38552852
DOI: 10.1016/j.bcp.2024.116172 -
Rheumatology (Oxford, England) Mar 2024To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM).
OBJECTIVES
To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM).
METHODS
. Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors of the damage were measured.
RESULTS
DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (-10% and -30% respectively) with a dispersion that varied widely (IQR -24.3% to + 7.8% and -51.3% to -18.9% respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, p= 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains), and blood-levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, functions impairment, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (AUC 0.71 and 0.80, respectively).
CONCLUSION
DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis.
PubMed: 38544289
DOI: 10.1093/rheumatology/keae207 -
Nutrients Mar 2024Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated...
BACKGROUND
Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects.
METHODS
A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach.
RESULTS
MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD.
CONCLUSIONS
We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.
Topics: Humans; Child; Animals; Horses; Osteonectin; Cross-Sectional Studies; Pediatric Obesity; HSP27 Heat-Shock Proteins; Non-alcoholic Fatty Liver Disease; Biomarkers; Cardiovascular Diseases; Lipids
PubMed: 38542777
DOI: 10.3390/nu16060866 -
International Immunopharmacology May 2024Inflammation and atherosclerosis (AS) are closely associated to Secreted Protein Acidic and Rich in Cysteine (SPARC) and its related factors. This study attempted to...
BACKGROUND AND AIMS
Inflammation and atherosclerosis (AS) are closely associated to Secreted Protein Acidic and Rich in Cysteine (SPARC) and its related factors. This study attempted to define the role and the potential mechanism of SPARC and its related factors in ameliorating hyperlipidemia and AS by aerobic exercise intervention.
METHODS
The AS rat model was established with a high-fat diet plus vitamin D3 intraperitoneal injection. Treadmill exercises training (5 days/week at 14 m/min for 60 min/day) for 6 weeks was carried out for AS rat intervention method. Western blotting and qRT-PCR were used to analyze the mRNA and protein expression of SPARC and its related factors, respectively. H&E staining was applied to evaluate the morphological changes and inflammation damage. Von Kossa staining was used to measure the degree of vascular calcification. Fluorescence immunohistochemistry staining was used to detect the expression and distribution of SPARC signal molecules.
RESULTS
SPARC was highly expressed and co-localization with the smooth muscle marker α-SMC in the AS rat. And its downstream factors, NF-κB, Caspase-1, IL-1β and IL-18 were upregulated (P < 0.05 or P < 0.01), FNDC5 expression was downregulated in AS rat model. However, slight declined body weight, delayed AS progression, decreased hyperlipidemia and favorable morphology of skeletal muscle and blood vessels have been detected in AS rat with aerobic exercise intervention. Moreover, the expression of SPARC and its downstream factors were decreased (P < 0.05 or P < 0.01), while elevated the expression of FNDC5 (P < 0.01) was observed after aerobic exercise intervention.
CONCLUSIONS
This study suggested that aerobic exercise ameliorated hyperlipidemia and AS by effectively inhibiting SPARC signal, and vascular smooth muscle cells may contribute greatly to the protection of AS.
Topics: Animals; Osteonectin; Atherosclerosis; Male; Physical Conditioning, Animal; Diet, High-Fat; Rats; Rats, Sprague-Dawley; Signal Transduction; Disease Models, Animal; Hyperlipidemias; Cholecalciferol
PubMed: 38537537
DOI: 10.1016/j.intimp.2024.111856