Disease relevance of Postn

• periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype [1].
• We found here that periostin mRNA expression is markedly downregulated in a variety of human cancer cell lines and human lung cancer tissues [2].
• Human cancer cell lines with reduced endogenous periostin gene expression that were infected with a recombinant retrovirus containing the periostin gene had reduced anchorage-independent growth [2].
• The establishment of the baculovirus expression system with a high productivity of recombinant OSF-2 (around 40 micrograms/ml at maximum) and its heparin binding properties should allow us to obtain large amounts of rmOSF-2 [3].
• The data suggest that in insulin-dependent diabetes mellitus the balance between beta cell destruction, associated with intra-islet infiltration, and nondestructive (potential protective) peri-islet insulitis may depend on both the antigens recognized, and the prevailing cytokine environment [4].

Psychiatry related information on Postn

• Our findings suggest that the time between PN 3 and PN 7 represents a critical period during which elements of the OPL are assembled [5].
• Mice that were selected for over 108 generations for body weight at the postnatal (PN) day 21 were examined in the open field (OF) test and in the Lashley maze (LM) for their exploratory behavior and spatial learning [6].

High impact information on Postn

• We find that Lpin1 null mutations lead to lipoatrophy of the epineurium, and to the dysregulation of a battery of genes required for the regulation of storage lipid metabolism in both the endoneurium and peri/epineurium [7].
• Adoptive transfer of these lines into neonatal mice confirms that overt diabetes is induced by gamma-IFN-secreting Th1 cells, whereas transfer of IL-4-secreting Th2 cells resulted in a nondestructive peri-islet insulitis [4].
• Twelve genes so identified were tested, and 10 (83%) showed appropriate expression in the external granular layer (EGL) of the postnatal day (PN) 7 cerebellum and down-regulation by PN 15, as verified by in situ hybridization [8].
• Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses [1].
• Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues [1].

Chemical compound and disease context of Postn

• An alternative explanation for glutamate-mediated injury is hypoxia due to peri-infarct spreading depression-like depolarizations [9].
• These data demonstrate an active role for periostin in EMT and metastasis that requires cross-talk between integrin and EGFR signaling pathways [10].
• The proinflammatory and potential neurotoxic cytokine tumor necrosis factor (TNF) is produced by activated CNS resident microglia and infiltrating blood-borne macrophages in infarct and peri-infarct areas following induction of focal cerebral ischemia [11].
• Reproductive toxicity of gamma-ethyl-gamma-phenyl-butyrolactone, a new anticonvulsant and hypnotic drug, in mice. Fertility and peri- and post-natal studies [12].
• These preliminary results suggest that peri-operative administration of nafamostat mesilate may prevent metastasis into the liver after surgery for gastrointestinal malignancies [13].

Biological context of Postn

• In situ hybridization studies for periostin [osteoblast-specific factor 2 (fasciclin I-like)] and biglycan revealed that these genes are restricted to mesenchymal derivatives during embryogenesis and are significantly regulated during regeneration of the injured hindlimb skeletal muscle [14].
• To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene [1].
• Both purified periostin protein and the periostin-Fc recombinant protein supported attachment and spreading of MC3T3-E1 cells, and this effect was impaired by antiperiostin antiserum, suggesting that periostin is involved in cell adhesion [15].
• We had previously identified the cDNA for a novel protein called osteoblast-specific factor 2 (OSF-2) from an MC3T3-E1 cDNA library using subtraction hybridization and differential screening techniques [15].
• Nucleotide sequence revealed four periostin transcripts that differ in the length of the C-terminal domain, possibly caused by alternative splicing events [15].

Anatomical context of Postn

• In the periostin-rich areas of jaw bones, but not in the long bones, portions of AAC-like mineralized layers were often replaced with and/or covered by acellular extrinsic fiber cementum (AEFC)-like tissue [16].
• Because TGF-beta has dramatic effects on periosteal expansion and the recruitment of osteoblast precursors, this factor was tested for its effects on periostin expression [15].
• Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta [15].
• Based on this observation and the fact that other proteins have been called OSF-2, the protein was renamed "periostin." Western blot analysis showed that periostin is a disulfide linked 90 kDa protein secreted by osteoblasts and osteoblast-like cell lines [15].
• Periostin mRNA is initially present within the E9.5 first branchial arch epithelium and then shifts to underlying ectomesenchyme [17].

Associations of Postn with chemical compounds

• Tunicamycin treatment of infected cells resulted in a mobility shift of OSF-2 (approximately 90-kDa band) on Western blots [3].
• These studies indicate that tumorigenic activity of methylated phenanthrenes requires inhibition of dihydrodiol formation at the K-region (9,10-positions) in addition to a bay-region methyl group and a free peri position, both adjacent to an unsubstituted angular ring [18].
• Odor deprivation and a decrease in functional activity in experimental bulbs was evident from deoxyglucose autoradiographs at PN 21 and PN 30 [19].
• The generation of peri-infarct spreading depressions and the associated metabolic workload can be suppressed by NMDA and non-NMDA antagonists [9].
• The expression of osteoblast-specific factor 2 and leukocyte 12/15 lipoxygenase, which are also expressed in LE under the control of P4, were not increased by LIF [20].

Regulatory relationships of Postn

• Spatiotemporal comparison of the fasciclin-containing secreted adhesion genes, TGFbeta induced clone H3 (betaigH3) and periostin, revealed that they are co-localized within the outflow tract endocardial cushions, but that betaigH3 expression is restricted to the septal cushions within the atrioventricular canal [21].

Other interactions of Postn

• Because tooth and periodontium development is a well-described genetic model for organogenesis governed by a reciprocal set of epithelial-mesenchymal interactions, thought to be controlled by various TGF-beta superfamily members, we investigated whether periostin is present during tooth morphogenesis [17].
• We suggest that periostin plays multiple roles as a primary responder molecule during tooth development and may be linked to deposition and organization of other extracellular matrix adhesion molecules during maintenance of the adult tooth, particularly at the sites of hard-soft tissue interface [17].
• Additionally, periostin expression has previously been shown to be significantly increased by both transforming growth factor beta-1(TGFbeta1) and bone morphogenetic protein (BMP)-2 [22].
• It has been well established that core binding factor a-1/osteoblast-specific factor-2 (cbfa1/osf2) is a key regulator of osteoblast differentiation and function, however, it is not known whether it can induce bone formation in vitro and in vivo [23].
• Unlike other mesenchymally derived cell lines, periostin expression is not regulated by FGF-2 in smooth muscle cells [24].

Analytical, diagnostic and therapeutic context of Postn

• By Western blot analysis, TGF-beta increased periostin expression in primary osteoblast cells [15].
• Electron microscopy revealed that the disappearance of the shear zone resulted from a failure in digestion of collagen fibers in the periostin-/- mice [25].
• Periostin is an extracellular matrix protein, and immunoelectron microscopy showed a close association of periostin with collagen fibrils in vivo [25].
• Histologic examination of allografts from treated and untreated recipients revealed a similar peri-islet infiltration on day 6 [26].
• IFN-gamma demonstrated a distinct distribution pattern, localizing in the peri-arteriolar lymphoid regions of the spleen, whereas IFN-beta immunofluorescence appeared diffusely in all areas [27].

References