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Bone & Joint Research Oct 2023Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study...
AIMS
Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.
METHODS
A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM using immunohistochemistry and immunofluorescence.
RESULTS
A total of 12 weeks after treatment, 0.5 μg/μl rHAM brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment.
CONCLUSION
We found that 0.5 μg/μl rHAM induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment.
PubMed: 37783468
DOI: 10.1302/2046-3758.1210.BJR-2023-0019.R1 -
Scientific Reports Sep 2023As one of the key, long-term occupied sites in the Southern Levant, Jericho was one of the most important early Neolithic centres to witness social and economic changes...
As one of the key, long-term occupied sites in the Southern Levant, Jericho was one of the most important early Neolithic centres to witness social and economic changes associated with the domestication of plants and animals. This study applies strontium (Sr/Sr), oxygen (δO) and carbon (δC) isotope analyses to the enamel of 52 human teeth from Pre-Pottery Neolithic (PPN) layers of Jericho to directly study human diet and mobility and investigate the degree of consolidation and the flexibility of social organization of Jericho society in the PPN period. The results indicate only two non-local individuals out of the 44 sampled inhabitants identified by strontium isotope analysis and are consistent with the presence of a largely sedentary community at PPN Jericho with no evidence for large-scale migration. We also construct strontium spatial baselines (Sr/Sr map) with local Sr/Sr signatures for the sites across the Southern Levant based on systematic compilation and analysis of available data. In addition, we apply proteomic analysis of sex-specific amelogenin peptides in tooth enamel for sex estimation of the sampled individuals (n = 44), the results of which showed a sex-biased ratio (more male than female detected in this sample pool) in Jericho society during the PPN period, which may be due to the limited sample size or selective ritual practices like particular burial zones used for specific groups. We also pretreated a batch of human bone samples recovered from PPNB Jericho for stable carbon and nitrogen isotope analyses for dietary investigations. However, the extracted collagen showed poor preservation and no valid δC or δN data were obtained.
Topics: Humans; Male; Animals; Female; Proteomics; Tooth; Strontium Isotopes; Burial; Carbon
PubMed: 37773428
DOI: 10.1038/s41598-023-43549-1 -
International Dental Journal Apr 2024The aim of this research was to compare the efficacy of the remineralising potential of self-assembling peptides (SAPs): Curodont Repair (P11-4), P26, and leucine-rich...
BACKGROUND
The aim of this research was to compare the efficacy of the remineralising potential of self-assembling peptides (SAPs): Curodont Repair (P11-4), P26, and leucine-rich amelogenin peptides (LRAP) with the standard 5% NaF varnish (Duraphat) on early enamel caries lesions (EECLs).
METHODS
A demineralising solution (DS) was used to create artificial EECLs in human dental enamel specimens, which were randomly allocated to treatment groups: P11-4; P26 solution; LRAP solution; 5% NaF varnish; and deionised water (DIW). Each specimen was subjected to 8 days of pH cycling. Specimens from each test group were subjected to microcomputed tomography (micro-CT) and nanomechanical testing to assess mineral density (MD), hardness (H), and elastic modulus (EM) properties of sound, demineralised, and treated enamel.
RESULTS
The mean MD percentage gain was highest in the P26 and P11-4 groups, followed by the LRAP, 5% NaF varnish, and DIW groups. There were statistically significant differences amongst groups. In the outer layer of EECLs, the EM and H were highest in P26 and P11-4 groups, followed by the LRAP and 5% NaF varnish. In the inner layer of EECLs, the EM and H were highest in P11-4 and P26 groups, indicative of enhanced penetration and remineralisation of the deeper parts of the artificial EECLs.
CONCLUSIONS
P26 and P11-4 SAPs are more effective than 5% NaF varnish in remineralising the depth of EECLs.
Topics: Humans; X-Ray Microtomography; Dental Enamel; Tooth Remineralization; Fluorides, Topical; Sodium Fluoride; Dental Caries; Peptides
PubMed: 37743135
DOI: 10.1016/j.identj.2023.07.003 -
Scientific Reports Sep 2023Skeletal remains discovered in Simon's Town, South Africa, were hypothesised as being associated with a former Dutch East India Company (VOC) hospital. We report a novel...
Skeletal remains discovered in Simon's Town, South Africa, were hypothesised as being associated with a former Dutch East India Company (VOC) hospital. We report a novel combined osteological and biochemical approach to these poorly-preserved remains. A combined strontium (Sr/Sr), oxygen (δO) and carbon (δC) isotope analysis informed possible childhood origins and diet, while sex-specific amelogenin enamel peptides revealed biological sex. Osteological analyses presented evidence of residual rickets, a healed trauma, dental pathological conditions, and pipe notches. The combined isotope analyses yielded results for 43 individuals which suggested a diverse range of geological origins, including at least 16% of the population being non-local. The inclusion of δC had intriguing implications for three individuals who likely did not have origins in the Cape Town region nor in Europe. Peptide analysis on the dental enamel of 25 tested individuals confirmed they were all biologically male. We suggest that isolated enamel may provide crucial information about individuals' pathological conditions, geographical origins, diet, and biological sex. These data further demonstrated that a combined approach using multiple osteological and biochemical methods is advantageous for human remains which are poorly preserved and can contextualise a site with little direct evidence.
Topics: Female; Humans; Male; Child; South Africa; Body Remains; Proteomics; Burial; Isotopes; India
PubMed: 37673940
DOI: 10.1038/s41598-023-41503-9 -
Journal of Materials Science. Materials... Sep 2023The aim of this study is to investigate a robust and stable calcium-phosphorus system to remineralize human early enamel caries lesions with nanocomplexes of...
The aim of this study is to investigate a robust and stable calcium-phosphorus system to remineralize human early enamel caries lesions with nanocomplexes of carboxymethyl chitosan/L-serine/amorphous calcium phosphate (CMC-Ser-ACP) to develop an effective method for mimicking the amelogenin (AMEL) mineralization pattern through ACP assembly. A CMC-Ser-ACP nanocomplex solution was first synthesized by a chemical precipitation method, and then 1% sodium hypochlorite (NaClO) was added to induce ACP phase formation. The morphologies of the nanocomplexes were characterized by transmission electron microscopy (TEM), and zeta potential analysis and Fourier transform infrared spectroscopy (FTIR) were performed to detect surface charge and functional group changes. The subtle changes of the demineralized enamel models induced by the remineralization effect were observed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The CMC-Ser-ACP nanocomplex solution could be preserved without any precipitation for 45 days. After the application of NaClO and through the guidance of Ser, ACP nanoparticles transformed into relatively orderly arranged hydroxyapatite (HAP) crystals, generating an aprismatic enamel-like layer closely integrated with the demineralized enamel, which resulted in enhanced mechanical properties for the treatment of early enamel caries lesions. The CMC-Ser-ACP nanocomplex solution is a remineralization system with great solution stability, and when NaClO is added, it can rapidly regenerate an aprismatic enamel-like layer in situ on the demineralized enamel surface. This novel remineralization system has stable chemical properties and can greatly increase the therapeutic effects against early enamel caries.
Topics: Humans; Chitosan; Amelogenin; Calcinosis; Dental Caries; Serine
PubMed: 37658964
DOI: 10.1007/s10856-023-06745-z -
Journal of Dental Research Oct 2023Amelogenin plays a crucial role in tooth enamel formation, and mutations on X-chromosomal amelogenin cause X-linked amelogenesis imperfecta (AI). Amelogenin...
Amelogenin plays a crucial role in tooth enamel formation, and mutations on X-chromosomal amelogenin cause X-linked amelogenesis imperfecta (AI). Amelogenin pre-messenger RNA (mRNA) is highly alternatively spliced, and during alternative splicing, exon4 is mostly skipped, leading to the formation of a microRNA (miR-exon4) that has been suggested to function in enamel and bone formation. While delivering the functional variation of amelogenin proteins, alternative splicing of exon4 is the decisive first step to producing miR-exon4. However, the factors that regulate the splicing of exon4 are not well understood. This study aimed to investigate the association between known mutations in exon4 and exon5 of X chromosome amelogenin that causes X-linked AI, the splicing of exon4, and miR-exon4 formation. Our results showed mutations in exon4 and exon5 of the amelogenin gene, including c.120T>C, c.152C>T, c.155C>G, and c.155delC, significantly affected the splicing of exon4 and subsequent miR-exon4 production. Using an amelogenin minigene transfected in HEK-293 cells, we observed increased inclusion of exon4 in amelogenin mRNA and reduced miR-exon4 production with these mutations. In silico analysis predicted that Ser/Arg-rich RNA splicing factor (SRSF) 2 and SRSF5 were the regulatory factors for exon4 and exon5 splicing, respectively. Electrophoretic mobility shift assay confirmed that SRSF2 binds to exon4 and SRSF5 binds to exon5, and mutations in each exon can alter SRSF binding. Transfection of the amelogenin minigene to LS8 ameloblastic cells suppressed expression of the known miR-exon4 direct targets, and , related to multiple pathways. Given the mutations on the minigene, the expression of has been significantly upregulated with c.155C>G and c.155delC mutations. Together, we confirmed that exon4 splicing is critical for miR-exon4 production, and mutations causing X-linked AI in exon4 and exon5 significantly affect exon4 splicing and following miR-exon4 production. The change in miR-exon4 would be an additional etiology of enamel defects seen in some X-linked AI.
Topics: Humans; Amelogenin; Amelogenesis Imperfecta; HEK293 Cells; Mutation; Dental Enamel Proteins; MicroRNAs; RNA, Messenger
PubMed: 37563801
DOI: 10.1177/00220345231180572 -
Scientific Reports Jul 2023Dental enamel is a peculiar biological tissue devoid of any self-renewal capacity as opposed to bone. Thus, a thorough understanding of enamel composition is essential...
Dental enamel is a peculiar biological tissue devoid of any self-renewal capacity as opposed to bone. Thus, a thorough understanding of enamel composition is essential to develop novel strategies for dental enamel repair. While the mineral found in bone and dental enamel is generally viewed as the biologically-produced equivalent of hydroxy(l)apatite, the formation of these bioapatites is controlled by different organic matrix frameworks-mainly type-I collagen in bone and amelogenin in enamel. In lower vertebrates, such as rodents, two distinct types of enamel are produced. Iron-containing pigmented enamel protects the continuously growing incisor teeth while magnesium-rich unpigmented enamel covers the molar teeth. Using high-resolution Raman spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy, this work explores the differences in acid phosphate (HPO), carbonate (CO), hydroxyl (OH), iron, and magnesium content of pigmented incisor enamel and unpigmented molar enamel of Sprague Dawley rats. Bundles of hydroxy(l)apatite nanowires comprise the enamel prisms, where prisms in pigmented enamel are wider and longer than those in unpigmented molars. In contrast to magnesium-rich unpigmented enamel, higher mineral crystallinity, and higher HPO and OH levels are hallmark features of iron-rich pigmented enamel. Furthermore, the apparent absence of iron oxides or oxy(hydroxides) indicates that iron is introduced into the apatite lattice at the expense of calcium, albeit in amounts that do not alter the Raman signatures of the PO internal modes. Compositional idiosyncrasies of iron-rich pigmented and nominally iron-free unpigmented enamel offer new insights into enamel biomineralisation supporting the notion that, in rodents, ameloblast function differs significantly between the incisors and the molars.
Topics: Rats; Animals; Rats, Sprague-Dawley; Incisor; Magnesium; Spectrum Analysis, Raman; Apatites
PubMed: 37516744
DOI: 10.1038/s41598-023-38792-5 -
Clinical Oral Investigations Sep 2023To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing / regeneration in recession-type defects.
OBJECTIVES
To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing / regeneration in recession-type defects.
MATERIALS AND METHODS
A total of 17 gingival recession-type defects were surgically created in the maxilla of three minipigs. The defects were randomly treated with a coronally advanced flap (CAF) and either rAmelX (test), or a CAF and placebo (control). At three months following reconstructive surgery, the animals were euthanized, and the healing outcomes histologically evaluated.
RESULTS
The test group yielded statistically significantly (p = 0.047) greater formation of cementum with inserting collagen fibers compared with the control group (i.e., 4.38 mm ± 0.36 mm vs. 3.48 mm ± 1.13 mm). Bone formation measured 2.15 mm ± 0.8 mm in the test group and 2.24 mm ± 1.23 mm in the control group, respectively, without a statistically significant difference (p = 0.94).
CONCLUSIONS
The present data have provided for the first-time evidence for the potential of rAmelX to promote regeneration of periodontal ligament and root cementum in recession-type defects, thus warranting further preclinical and clinical testing.
CLINICAL RELEVANCE
The present results set the basis for the potential clinical application of rAmelX in reconstructive periodontal surgery.
Topics: Humans; Animals; Swine; Amelogenin; Swine, Miniature; Gingival Recession; Wound Healing; Dental Cementum; Treatment Outcome; Tooth Root; Connective Tissue
PubMed: 37421492
DOI: 10.1007/s00784-023-05123-x -
Scientific Reports Jul 2023Given the absence of written records, the main source of information available to analyze gender inequalities in early complex societies is the human body itself. And...
Given the absence of written records, the main source of information available to analyze gender inequalities in early complex societies is the human body itself. And yet, for decades, archaeologists have struggled with the sex estimation of poorly preserved human remains. Here we present an exceptional case study that shows how ground-breaking new scientific methods may address this problem. Through the analysis of sexually dimorphic amelogenin peptides in tooth enamel, we establish that the most socially prominent person of the Iberian Copper Age (c. 3200-2200 BC) was not male, as previously thought, but female. The analysis of this woman, discovered in 2008 at Valencina, Spain, reveals that she was a leading social figure at a time where no male attained a remotely comparable social position. Only other women buried a short time after in the Montelirio tholos, part of the same burial area, appear to have enjoyed a similarly high social position. Our results invite to reconsider established interpretations about the political role of women at the onset of early social complexity, and question traditionally held views of the past. Furthermore, this study anticipates the changes that newly developed scientific methods may bring to prehistoric archaeology and the study of human social evolution.
Topics: Humans; Female; Amelogenin; Leadership; Peptides; Spain; Archaeology
PubMed: 37414858
DOI: 10.1038/s41598-023-36368-x -
BMC Psychiatry Jun 2023Schizophrenia (SCZ) has a global prevalence of 1% and increases the risk of mortality, reducing life expectancy. There is growing evidence that the risk of this disorder...
BACKGROUND
Schizophrenia (SCZ) has a global prevalence of 1% and increases the risk of mortality, reducing life expectancy. There is growing evidence that the risk of this disorder is higher in males than in females and it tends to develop in early adulthood. The Y chromosome is thought to be involved in biological processes other than sex determination and spermatogenesis. Studies have shown that loss of chromosome Y (LOY) in peripheral blood cells is associated with a variety of diseases (including cancer) and increased all-cause mortality. An analysis of the relationship between LOY and schizophrenia is warranted.
METHODS
A total of 442 Chinese males (271 patients with schizophrenia vs. 171 controls) were included in this study. The copy numbers of the Y and X chromosomes were detected by positive droplets targeting the amelogenin gene (AMEL) on the Y chromosome and X chromosome (AMELY and AMELX, respectively), using droplet digital PCR (ddPCR). The LOY percentage was defined as the difference between the concentration of AMELX and the concentration of AMELY divided by the concentration of AMELX, denoted as (X - Y)/X.
RESULTS
In the Han Chinese population, the LOY percentage was higher in the schizophrenia group than in the control group (p < 0.05), although there was no significant difference in the presence of LOY between the two groups. A strong correlation was found between the average of the disease duration and the average of the LOY percentage (R = 0.506, p = 0.032). The logistic regression analysis implied that the risk of LOY increases by 0.058 and 0.057 per year according to age at onset and duration of disease, respectively (p = 0.013, p = 0.017).
CONCLUSIONS
In the Han Chinese population, the LOY percentage of the disease group was significantly different from that of the control group. The age of onset and duration of schizophrenia might be risk factors for LOY in peripheral blood cells. A larger sample size and expanded clinical information are needed for more in-depth and specific analyses.
Topics: Adult; Humans; Male; Blood Cells; Chromosomes, Human, Y; East Asian People; Schizophrenia
PubMed: 37370034
DOI: 10.1186/s12888-023-04929-z