Rôle des isoformes des récepteurs de l'hormone thyroïdienne dans la physiologie osseuse

Les désordres thyroidiens sont la cause de sévères altérations du développement, de la maturation et de l'ossification chez l'enfant et du maintien de la masse osseuse chez l'adulte. Les gènes Thra et Thrb codent différents isoformes de récepteurs de l'hormone thyroidienne capables de réguler l'expression génique en réponse à T3 (TRa2, TRb1, TRb2). Pour comprendre les mécanismes moléculaires et identifier le rôle des isoformes dans la maturation et du remodelage osseux (différenciation, expression, prolifération), nous avons étudié les phénotypes squelettiques d'animaux invalidés pour l'un ou l'autre de ces gènes (TRa0/0, TRb-/- et in vitro l'effet de ces mutations dans l'action de l'hormone thyroidienne sur la différenciation et la prolifération des chondrocytes. Ainsi, nous avons pu mettre en évidence le rôle majeur de TRb dans la différenciation chondrocytaire et une augmentation du turnover chez les souris TRa se manifestant par l'augmentation de leur masse osseuse.Childhood hypothyroidism results in severely skeletal development and adult thyrotoxicosis causes osteoporosis. To investigate molecular mechanism underlying these abnormalities we characterized the skeletal phenotypes of mice lacking either thyroid hormone receptor a or b (TRa 0/0, TRb-/-) and leaded in vitro chondrocytes studies. During growth, absence of TRa in TRa0/0 mice, resulted in skeletal hypothyroidism, growth retardation, delayed ossification and reduced calcified bone and, lack of TRb resulted in skeletal hyperthyroidism, accelerated growth, advanced ossification and increased calcification. Adult TRa0/0 mice have osteosclerosis, whereas TRb-/- were osteoporotic. Elsewhere, TRb appears to be necessary for T3-induced differenciation of chondrocytes compare to the TRa. The gene TRa appears as a major regulator of skeletal development and bone mineral accrual and in the maintenance of adult bone structure and mineralization.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Thyroid hormones regulate fibroblast growth factor receptor signaling during chondrogenesis

International audienc

Regulation of corneal keratin-12 gene expression by the human Krüppel-like transcription factor 6.

International audienceThe keratin-12 (K12) protein is essential for the integrity of the corneal epithelium. This study was conducted to investigate the possible involvement of Krüppel-like factor 6 (KLF6) in the corneal regulation of K12 gene expression, in view of the presence of one KLF6 potential binding site in the human K12 promoter and the known role of KLF6 in regulating keratin gene expression

Eléments traces métalliques et métalloïdes dans les romarins sur le massif des Calanques (Marseille): transferts dans les parties consommées et effets sur la composition chimique des huiles essentielles

National audienc

Incidence and preventability of hospital admissions for adverse drug reactions in France: A prospective observational study (IATROSTAT)

International audienceAims: In the last French study in 2007, the incidence of hospital admissions (HAs) related to adverse drug reactions (ADRs) was 3.6%. The objective was to assess the current ADR-HA incidence in France and to describe both its characteristics and preventability.Methods: A prospective multicentre study was conducted among randomly selected French public hospital medical wards (April-July 2018). Patients admitted during a week period were included. ADR-HA cases were collected by the French Regional Pharmacovigilance Centres network. An independent committee validated potential cases and ADR preventability.Results: ADR-HA incidence was 8.5% (95% confidence interval [CI]: 7.6-9.4%), increasing with age (3.3% [95%CI: 1.8-5.5%] ≤16 y vs. 10.6% [95%CI: 9.3-12.0%] ≥65 y). The most common ADRs were haemorrhagic events (8.8%), haematological disorders (6.5%), acute renal failure (6.3%), fluid and electrolyte disorders (6.0%), and falls (5.2%). New drugs were involved: targeted therapies (22.8% of antineoplastics), direct oral anticoagulants (29.6% of antithrombotics) and incretin-based drugs (20.0% of antidiabetics). ADRs were preventable in 16.1% of cases because the drugs involved had not been used in accordance with monographies, package leaflets or other therapeutic guidelines. The main situations of noncompliance addressed either dose or duration of use (27.9%), warning (23.2%), use precaution (18.6%) and inappropriate self-medication or misuse by patients (11.6%).Conclusion: In France, ADR-HA incidence dramatically increased over the last decade. A significant proportion was related to new pharmacological classes and considered as preventable. These findings should lead to in-depth thought on preventive actions on at-risk drug classes

<i>Ex vivo</i> differentiation of bone marrow osteoblast precursors originating from ERRαKO mice.

<p><b>A</b>) Upper panels: Alkaline phosphatase (ALP)- and von Kossa staining after 7 d and 21 d, respectively, in differentiation medium. Lower panel: expression of osteoblast differentiation markers measured by QPCR after 7 d in differentiation medium. Data are expressed relative to wild type level. Ocn: osteocalcin; opn: osteopontin. <b>B</b>) Time course of ALP expression after switch to differentation medium in wild type- (white bars) and ERRαKO- (black bars) originating cells measured by QPCR. Data are expressed relative to wild type level at d0. <b>C</b>) Rescue of the differentiation phenotype by infection with an ERRα-encoding <i>vs</i> a GFP-encoding adenovirus. Upper panel: ALP staining; lower panel: expression of osteoblast differentiation markers determined by QPCR. Adenoviruses were added together with the differentiation medium and the experiment was stopped after 7 d. Data are expressed relative to AdGFP infected cells. <b>D</b>) Proliferation of osteoblast precursors. Upper left panel: time course of cell number; lower left panel: time course of ALP staining; right panel: time course of ALP enzymatic activity relative to protein content. Time is indicated after switch to differentiation medium. All experiments were performed at least three times using female bone marrow. Staining views represent a single typical experiment; expression data and cell counting represent a typical experiment performed in triplicate with error bars indicating S.D.</p