Search

Background: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy., Objectives: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR., Methods: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics., Results: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%)., Conclusion: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MJG: Consultant, speaker and/or advisory boards for AbbVie, Akros Pharma, Amgen, Arcutis, Aslan, Aristea, AnaptysBio, Boehringer Ingelheim, BMS, Celgene, Dermira, Dermavant, Eli Lilly and Company, Galderma SA, GSK, Incyte, Janssen, Kyowa Kirin, Leo Pharma, MedImmune, Merck, Moonlake, Meiji, Nimbus, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi Genzyme, and UCB; RB: Advisory Board Member, Consultant, Speaker and/or Investigator for and received honoraria and/or grants from, AbbVie, Alumis, Amgen, AnaptysBio, Bausch Health, Boston, BMS/Celgene, Dermavant, Eli Lilly, Janssen, LEO Pharma, Nimbus, Novartis, Pfizer, Regeneron, UCB, VentyxBio and Xencor. R Bissonnette is also an employee and shareholder of Innovaderm Research; SK: Consultant, speaker or advisory boards for AbbVie, Actelion Pharmaceuticals, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly and Company, Galderma SA, GSK, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, UCB, and Valeant Pharmaceutical; KAP: Receive honoraria and/ or clinical research grants as a consultant, speaker, scientific officer, steering committee member, and/or advisory board member for 3M, AbbVie, Akesis, Akros, Alza, Amgen, Astellas, Baxter, Boehringer Ingelheim, Celgene, Centocor, Cipher, Eli Lilly, Forward Pharma, Funxional Therapeutics, Galderma, Glaxo Smith Kline, Isotechnika, Janssen, Janssen Biotech, Kirin, Kyowa, Lypanosys, Merck-Serono, Merck Sharpe Dome, Mitsubishi Pharma, Novartis, Pfizer, Takeda, UCB, Vertex, and/ or Wyeth; LCG: Consultant, speaker, and received grants for clinical research from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Merck, Novartis, Pfizer, and Valeant; speaker and consultant for Aralez; consultant and received grants for clinical research from Bristol-Meyers Squibb, and received grants for clinical research from Boehringer Ingelheim and UCB. WPG: grants/research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer; honoraria for ad boards/invited talks/consultation from AbbVie, Actelion, Amgen, Arylide, Bausch Health, Boehringer, Celgene, Cipher, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, PeerVoice, Pfizer, Sanofi-Genzyme, Tribute, UCB, Valeant; and clinical trials (study fees) from AbbVie, Asana Biosciences, Astellas, Boerhinger-Ingleheim, Celgene, Corrona/National Psoriasis Foundation, Devonian, Eli Lilly, Galapagos, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, UCB.>.; VH: Consultant, speaker or advisory boards for Abbvie, Eli Lilly, Janssen, and Novartis; NHS: Consultant for AbbVie, Bausch Medicine, Celgene, Janssen, Leo Pharma, Lilly, Novartis, Sanofi Genzyme; RV: Consultant, speaker and/or advisory boards for AbbVie, Actelion Pharmaceuticals, Amgen, Boehringer Ingelheim, BMS, Celgene, Dermira, Eli Lilly and Company, Galderma SA, GSK, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, UCB, and Valeant Pharmaceutical; RG: clinical trials for AbbVie, Bausch Health, and Janssen and has received honoraria as consultant and/or speaker from AbbVie, Bausch Health, Eli Lilly, Janssen, Kyowa Kirin, Mallinckrodt, Novartis, Sun Pharma and Sanofi; VHP: Consultant, speaker and/or advisory boards for AbbVie, Actelion, Amgen, AnaptysBio, Aralez, Arcutis, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, Janssen, LEO Pharma, L’Oreal, Medexus, Novartis, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB Pharma, and Valeant; investigator for AbbVie, Amgen, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Nimbus Lakshmi, Novartis, Pfizer, Regeneron, Reistone, Sanofi Genzyme, UCB Pharma, and Valeant; received educational grants from AbbVie, Bausch Health, Celgene, Janssen, LEO Pharma, Novartis, Sanofi Genzyme, and Valeant; IT: Consultant, speaker or investigator for Abbvie, Amgen, Arcutis, Aristea, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kiniksa, LeoPharma, Mallinckrodt, Novartis, Pfizer, Sanofi, SunPharma, UCB; WL, KP, SDS, NA and OL: Employee of either Janssen Research & Development or Janssen Inc. Canada; RA: Consultant, speaker or advisory boards for Abbvie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Galderma, Janssen, Leo Pharma, Novartis, Pfizer, Sandoz, Sanofi, Sun pharma, and UCB.

Amelotin (AMTN) is a recently discovered protein that is specifically expressed during the maturation stage of dental enamel formation. It is localized at the interface between the enamel surface and the apical surface of ameloblasts. AMTN knock-out mice have hypomineralized enamel, whereas transgenic mice overexpressing AMTN have a compact but disorganized enamel hydroxyapatite (HA) microstructure, indicating a possible involvement of AMTN in regulating HA mineralization directly. In this study, we demonstrated that recombinant human (rh) AMTN dissolved in a metastable buffer system, based on light scattering measurements, promotes HA precipitation. The mineral precipitates were characterized by scanning and transmission electron microscopy and electron diffraction. Colloidal gold immunolabeling of AMTN in the mineral deposits showed that protein molecules were associated with HA crystals. The binding affinity of rh-AMTN to HA was found to be comparable to that of amelogenin, the major protein of the forming enamel matrix. Overexpression of AMTN in mouse calvaria cells also increased the formation of calcium deposits in the culture medium. Overexpression of AMTN during the secretory stage of enamel formation in vivo resulted in rapid and uncontrolled enamel mineralization. Site-specific mutagenesis of the potential serine phosphorylation motif SSEEL reduced the in vitro mineral precipitation to less than 25%, revealing that this motif is important for the HA mineralizing function of the protein. A synthetic short peptide containing the SSEEL motif was only able to facilitate mineralization in its phosphorylated form ((P)S(P) SEEL), indicating that this motif is necessary but not sufficient for the mineralizing properties of AMTN. These findings demonstrate that AMTN has a direct influence on biomineralization by promoting HA mineralization and suggest a critical role for AMTN in the formation of the compact aprismatic enamel surface layer during the maturation stage of amelogenesis., (© 2014 American Society for Bone and Mineral Research.)

Enamel, covering the surface of teeth, is the hardest substance in mammals. It is designed to last a lifetime in spite of severe environmental challenges. Enamel is formed in a biomineralization process that is essentially divided into secretory and maturation stages. While the molecular events of enamel formation during the secretory stage have been elucidated to some extent, the mechanisms of enamel maturation are less defined, and little is known about the molecules present beyond the maturation stage. Several genes, all located within the secreted calcium-binding phosphoprotein (SCPP) gene cluster, were recently shown to be expressed during the developmental continuum from maturation stage ameloblasts to junctional epithelium (JE). This review introduces four such genes and their protein products, and presents our current state of knowledge on their roles, primarily in enamel formation and JE biology. The discovery of these proteins, and a more detailed analysis of their biological functions, will likely contribute to a more thorough understanding of the molecular mechanisms of enamel maturation and dentogingival attachment.