Hck contributes to bone homeostasis by controlling the recruitment of osteoclast precursors

ABSTRACT In osteoclasts, Src controls podosome organization and bone degradation, which leads to an osteopetrotic phenotype in src ؊/؊ mice. Since this phenotype was even more severe in src ؊/؊ hck ؊/؊ mice, we examined the individual contribution of Hck in bone homeostasis. Compared to wt mice, hck ؊/؊ mice exhibited an osteopetrotic phenotype characterized by an increased density of trabecular bone and decreased bone degradation, although osteoclastogenesis was not impaired. Podosome organization and matrix degradation were found to be defective in hck ؊/؊ osteoclast precursors (preosteoclast) but were normal in mature hck ؊/؊ osteoclasts, probably through compensation by Src, which was specifically overexpressed in mature osteoclasts. As a consequence of podosome defects, the 3-dimensional migration of hck ؊/؊ preosteoclasts was strongly affected in vitro. In vivo, this translated by altered bone homing of preosteoclasts in hck ؊/؊ mice: in metatarsals of 1-wk-old mice, when bone formation strongly depends on the recruitment of these cells, reduced numbers of osteoclasts and abnormal developing trabecular bone were observed. This phenotype was still detectable in adults. In summmary, Hck is one of the very few effectors of preosteoclast recruitment described to date and thereby plays a critical role in bone remodeling.-Vérollet, C., Gallois, A., Dacquin, R., Lastrucci, C., Pandruvada, S. M. N., Ortega, N., Poincloux, R., Behar, A., Cougoule, C., Lowell, C., Al Saati, T., Jurdic, P., Maridonneau-Parini, I. Hck contributes to bone homeostasis by controlling the recruitment of osteoclast precursors. FASEB J. 27, 3608 -3618 (2013). www.fasebj.org Key Words: osteopetrosis ⅐ cell migration ⅐ podosomes ⅐ Src tyrosine kinases Bone is renewed continuously by a process known as bone remodeling. Bone remodeling is accomplished by 3 cell types: osteocytes, osteoblasts, and osteoclasts (OCs). Osteocytes are the mechanical sensors of bone that regulate osteoclast formation. Osteoblasts synthetize the matrix and promote its mineralization, while OCs are responsible for degradation of bones during bone development, homeostasis, and repair. The formation and degradation of bone are tightly balanced in both time and space. A dysregulation of this tight balance between bone formation and bone degradation may result either in loss of bone mass, such as in osteoporosis, or in contrast, in a progressive increase in bone mass, such as in osteopetrosis. Degrading OCs are large multinucleated giant cells formed by the differentiation and fusion of mononuclear monocyte lineage precursors after stimulation by receptor activator of nuclear factor -B ligand (RANKL) and macrophage colony-stimulationg factor (M-CSF) (1-3). They are characterized by high levels of cathepsin K and tartrate resistant acidic phosphatase (TRAP) activities, whic

Donnees nouvelles sur la secretion pheromonale de Cryptophlebia leucotreta (Meyr). Lepidoptera Tortricidae

Dans des conditions de photopériode artificielle de jour long (16 : 8), les femelles de Cryptophlebia leucotreta émergent 1 heure après le début de la photophase et présentent un comportement d’appel sexuel à la 4e heure de la scotophase suivante. Une réévaluation de la sécrétion phéromonale de cette espèce a été faite par GC, GC-MS et microchimie. Il apparaît que la femelle émet à distance une phéromone composée d’acétoxy-1 dodécène-8-E (E8DDA) d’acétoxy-1 dodécène-8-Z (Z8DDA) et d'acétoxy-1 dodécane (C12OAc), dans les proportions suivantes : 69, 23 et 8 p. 100. Eprouvé sur les mâles en olfactomètre et en tunnel de vol, le mélange formé des 3 composés identifiés provoque des réponses supérieures à celles induites par le mélange E8/Z8DDA. Il s’est par ailleurs avéré que des mâles âgés de 5 jours répondaient bien mieux à la phéromone que des mâles âgés de 2 jours, bien que ceux-ci aient déjà atteint la maturité sexuelle. Une hypothèse expliquant ce résultat est proposée.New results on the sex pheromone of the false codling moth, Cryptophlebia leucotreta Meyr. (Lepidoptera, Tortricidae). Under laboratory conditions (light period : 16 h, dark period : 8 h), female Cryptophlebia leucotreta emerge 1 h after the beginning of the light phase and calling behaviour begins at the 4th hour of the following dark phase. It has been shown by GC, GC-MS and microchemical analysis that the sex pheromone of this species is a blend of E-8 dodecen-1-yl acetate (E8DDA), Z-8-dodecen-1-yl acetate (Z8DDA) and dodecyl acetate (C12OAc) in the ratio 69 :23 : 8. This ratio has been determined by collecting the effluvia emitted by the females with Porapak Q as adsorbent. Other extraction techniques (crude extracts and microencapsulation technique) gave similar data, except for C12OAc which was found in larger amounts. Behavioural tests (olfactometer and wind tunnel) have shown that the 3-component blend is more efficient in giving a male response than the blend containing only E8/Z8DDA. Further experiments have demonstrated that the responsiveness to synthetic pheromones is better for 5-day-old males than for 2-day-old males, although the latter are sexually mature. A hypothesis explaining this result is proposed

Absolute configuration of eldanolide, the wing gland pheromone of the male african sugar-cane borer, Eldona saccharina (Wlk) syntheses of its (+) and (-) enantiomers

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