Disease relevance of Skull

• Both OAF and PTH inhibit collagen synthesis in fetal rat calvaria at the concentrations that stimulate bone resorption [1].
• We have identified Twist target genes using human mutant calvaria osteoblastic cells from a child with Saethre-Chotzen syndrome with a Twist mutation that introduces a stop codon upstream of the bHLH domain [2].
• Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects [3].
• These studies demonstrate the expression of the key inflammatory cytokine interleukin-6 by osteoblasts in organ cultures of neonatal mouse calvaria, and in vivo using a mouse model that closely resembles the pathology of trauma-induced staphylococcal osteomyelitis, as determined by confocal microscopic analysis [4].
• We have shown previously that the hypomineralization defects of the calvarium and vertebrae of tissue nonspecific alkaline phosphatase (TNAP)-deficient (Akp2-/-) hypophosphatasia mice are rescued by simultaneous deletion of the Enpp1 gene, which encodes nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) [5].

High impact information on Skull

• Lovastatin and simvastatin increased bone formation when injected subcutaneously over the calvaria of mice and increased cancellous bone volume when orally administered to rats [6].
• High-resolution fluorine-19 spectra of halothane, methoxyflurane, and isoflurane were obtained with a surface coil centered over the calvarium [7].
• Cytosol fractions were prepared from fetal rat or embryonic chick calvaria and analyzed for binding of vitamin D3 metabolites on sucrose density gradients [8].
• Localized TIMP RNA was first detected at 13.5 days post conceptus (p.c.) in tissues undergoing osteogenesis, such as the mandible, ribs, and calvaria [9].
• Similarly, intramembranous bone formation on the calvaria was reduced 60% in COX-2(-/-) mice following in vivo injection of FGF-1 compared with either COX-1(-/-) or wild-type mice [10].

Chemical compound and disease context of Skull

• Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria [11].
• Alendronate inhibition of bone resorption in mouse calvaria also is blocked by mevalonate whereas clodronate inhibition is not [12].
• Although the effect of thyroid hormones on PG release from cultured calvaria was completely abolished by 5 x 10(-7) mol/liter indomethacin, in some experiments indomethacin reduced thyroid hormone-mediated bone resorption by only 50% [13].
• When LTB4 was injected over the calvaria of mice, there was a significant increase in bone resorption, osteoclast numbers, and eroded surfaces [14].
• Dose-response curves were prepared for in vitro bone resorption induced in neonatal mouse calvaria by tumor extract, bPTH-(1-34), and prostaglandin E2 [15].

Biological context of Skull

• Furthermore, we could also show that overexpression of FGF2 in transgenic mice leads to increased apoptosis in their calvaria [16].
• During skull development, disruption of TGFbeta signaling in the CNC severely impairs cell proliferation in the dura mater, consequently resulting in calvaria agenesis [3].
• We show that mice with Tgfbr2 conditional gene ablation in the CNC have complete cleft secondary palate, calvaria agenesis, and other skull defects with complete phenotype penetrance [3].
• We now report the isolation of a 1397-base pair (bp) full-length TRAP/tartrate-resistant acid ATPase (TrATPase) cDNA clone from a neonatal rat calvaria lambda gt11 cDNA library [17].
• These results also suggest that endogenous BMP-2 expression in fetal rat calvaria cells is important for bone cell differentiation [18].

Anatomical context of Skull

• The non-tumor-derived established bone cell lines (RCB 2.2A, RCB 2.2B, RCB 2.2C, RCB 2.2D) showed low basal 1,25-(OH)2D3 binding levels and no change in response to RA, while first subcultures of bone cell populations derived from fetal and neonatal rat calvaria showed decreased 1,25-(OH)2D3 binding, following similar treatment with RA [19].
• To determine whether 1,25(OH)2D3 increased TGF-beta production by bone cells, we treated mouse calvaria for 6 days and mouse osteoblasts for 2 days with 10 nM 1,25(OH)2D3 [20].
• Osteoclast activity, measured using a rat neonatal calvaria assay, increased in the presence of nelfinavir (NFV; 47.2%, p = 0.001), indinavir (34.6%, p = 0.001), saquinavir (24.3%, p = 0.001), or ritonavir (18%, p < 0.01) [21].
• 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited type I collagen synthesis in the central bone but not the periosteum of fetal rat calvaria maintained in organ culture [22].
• Vitamin K2 was able to induce bone markers in primary osteocytes isolated from wild-type murine calvaria but not in cells isolated from mice deficient in the SXR ortholog PXR [23].

Associations of Skull with chemical compounds

• Furthermore, A23187 at 1.0 mug/ml had no effect on the accumulation of cyclic AMP in the medium of either control, PTH- or calcitonin treated calvaria [24].
• The effects of both TGF-alpha and EGF in calvaria, but not those of parathyroid hormone, were inhibited by 5 X 10(-7) M indomethacin [25].
• 0.5 microM indomethacin inhibited milrinone effects in calvaria but usually not in limb bones [26].
• In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones [26].
• We find similarities between milrinone and thyroxine actions on bone, because prostaglandin production was crucial for the effects of both agents in calvaria but not in limb bones, and neither agent exhibited escape from calcitonin inhibition [26].

Gene context of Skull

• When the OBs were differentiated in vitro by treatment with bone morphogenic protein 2, the OBs from TIEG(+/+) calvaria displayed several mineralized nodules in culture, whereas those from TIEG(-/-) mice showed no nodules [27].
• Expression of E2A and FGFR3 was seen at the location of osteoblast differentiation in the calvaria of mouse embryos, implicating bHLH molecules in physiological osteoblast differentiation [28].
• The concentrations of IL-1 beta were high enough to induce bone resorption in the newborn mouse calvaria assay and the BRA was totally abolished by pretreatment of the supernatants with anti-IL-1 beta antibody but not with either anti-IL-1 alpha antibody or normal serum [29].
• We also carried out a detailed expression analysis of the helix-loop-helix factors (HLH) Twist and Id1 during calvaria and suture development (E10-P6) [30].
• Dlx5 may perform a general role in skeletal differentiation, as exemplified by hypomineralization within the calvaria [31].

Analytical, diagnostic and therapeutic context of Skull

• Using the reverse transcriptase/polymerase chain reaction (RT/PCR) and ribonuclease protection assays, we found that Pex/PEX mRNA is expressed predominantly in human fetal and adult mouse calvaria and long bone [32].
• Both in calvaria and in marrow cell culture, extensive expression of OPN, BSP, type I collagen (COL I), and ALP coincided with the onset of mineralization, and OC expression was observed after mineralized tissue formation [33].
• Utilization of FPLC-separated collagenase isozymes for the cell isolation increased the total cell yield to 1.50 million cells/calvarium [34].
• Three cysteine-dependent proteolytic activities were separated from a homogenate of mouse calvaria by a fractionation procedure involving (NH4)2SO4 precipitation, gel filtration and ion-exchange chromatography [35].
• Northern-blot analysis showed that the mRNAs of bone morphogenetic protein-2 and -4 were expressed in the calvaria [36].

References