Disease relevance of LOC395210

• In situ hybridization analysis of epiphyseal growth plates from chicken or mice homozygous for the Achondroplasia, G369C/mFGFR3 mutation demonstrated co-localization of OPN expression and osteoclast activity, as evidenced by tartarate resistant acid phosphatase positive cells in the osteochondral junction [1].
• Together, these findings support a strategy designed to target osteopontin in the context of prostate cancer therapy [2].
• Over time, osteopontin expressing dysplastic cells seemed to increase in number in high-grade PIN and increased further in adenocarcinoma, and in metastasis, almost all of the cancer cells immunohistochemically stained positive for osteopontin overexpression [2].
• Osteopontin alterations occurred early in the disease with dysregulated expression observed in lesions of low-grade prostatic intraepithelial neoplasia (PIN) [2].
• Our results demonstrate that osteopontin stimulates gelsolin-associated Src, leading to increased gelsolin-associated PI 3-kinase activity and PtdIns 3,4,5-P3 levels, which facilitate actin filament formation, osteoclast motility, and bone resorption [3].

High impact information on LOC395210

• We examined the biological properties of human prostate cancer cell lines LNCaP and PC-3, in which osteopontin overexpression was achieved via lentiviral gene transduction [2].
• Furthermore, excess osteopontin induced the LNCaP cells to acquire a strong intravasation potential in vivo in the chicken embryo chorioallantoic membrane assay for blood vessel penetration [2].
• Mechanistically, 10 nM BAG 75 marginally slowed, but did not block, the association of bone particles with chicken osteoclasts compared with osteopontin or control media [4].
• By contrast, other phosphoproteins similarly isolated from bone were less effective in inhibiting resorption with IC50 = 100 nM osteopontin and IC50 greater than 100 nM bone sialoprotein [4].
• In the present study, we show that osteopontin (OPN), a proinflammatory mediator involved in tissue repair, induces IL-1beta up-regulation in human monocytes [5].

Biological context of LOC395210

• Characterization of a cDNA for chicken osteopontin: expression during bone development, osteoblast differentiation, and tissue distribution [6].
• cDNA cloning and gene expression of chicken osteopontin. Expression of osteopontin mRNA in chondrocytes is enhanced by trypsin treatment of cells [7].
• An increased level of osteopontin mRNA in quail chondrocytes constitutively expressing v-myc oncogene is also shown [7].
• To further define the exact locations of the phosphorylated amino acids and the surrounding amino acid sequences, OPN was digested with trypsin, which generated seven major 32P-labeled peptides whose amino acid sequences were determined [8].
• We found that thiol depletion causes a decrease in the expression of osteopontin, type X and type II collagen and a significant loss of alkaline phosphatase activity, suggesting that the expression of the hypertrophic phenotype is tightly regulated by redox levels in chondrocytes [9].

Anatomical context of LOC395210

• A cDNA clone, pCP15, specific for the chicken 66-kDa major bone phosphoprotein (osteopontin), was isolated from a subtracted library enriched in DNAs coding for mRNAs expressed in chicken differentiating chondrocytes [7].
• Northern blot analysis of RNAs extracted from several chick embryo tissues and organs, confirm and extend the observation that osteopontin mRNA expression is not restricted to tissues involved in phosphate metabolism [7].
• The steady state level of osteopontin mRNA was enhanced by trypsin treatment of cultured cells [7].
• FGF upregulates osteopontin in epiphyseal growth plate chondrocytes: implications for endochondral ossification [1].
• Inhibition of PI 3-kinase activity by wortmannin blocks osteopontin stimulation of actin filament formation, suggesting that activation of gelsolin-associated PI 3-kinase is an important pathway in cytoskeletal regulation [3].

Associations of LOC395210 with chemical compounds

• Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts [10].
• Synthetic osteopontin and peptides from the osteopontin and bone sialoprotein sequences containing Arg-Gly-Asp stimulated immediate reductions in osteoclast cytosolic Ca2+ [10].
• OPN binding to alpha v beta 3 results in the rapid production of the phosphoinositides (PtdInsP), including phosphatidylinositol triphosphate (PtdIns 3,4,5P3) [11].
• The younger embryonic cell population showed 2- and 5-fold inductions of osteocalcin and osteopontin gene expression, respectively, and a 25% inhibition of collagen gene expression when treated with 1,25-(OH)2D3 [12].
• Tamoxifen did seem to reduce mRNA for collagen type I, but not bone sialoprotein, osteopontin, and osteocalcin [13].

Physical interactions of LOC395210

• Our data strongly suggest that osteopontin is an osteoclast autocrine motility factor binding to avb3 and CD44 during stimulation of osteoclast migration [14].
• We have shown that osteopontin binding to integrin alphav beta3 in osteoclasts stimulates gelsolin-associated phosphatidylinositol (PtdIns) 3-hydroxyl kinase (PI 3-kinase), leading to increased levels of gelsolin-bound PtdIns 3,4-P2, PtdIns 4,5-P2, and PtdIns 3, 4,5-P3, uncapping of barbed end actin, and actin filament formation [3].

Regulatory relationships of LOC395210

• The integrin alpha(v)beta(3) and CD44 regulate the actions of osteopontin on osteoclast motility [14].

Other interactions of LOC395210

• In addition, the migratory effects of osteopontin on osteoclasts were also mediated through CD44 receptors since blocking antibodies to CD44 blocked stimulation of motility [14].
• Comparison of two phosphoproteins in chicken bone and their similarities to the mammalian bone proteins, osteopontin and bone sialoprotein II [15].
• FGF and TGF beta, but not IGF-I or IGF-II, also caused phosphorylation of osteopontin [16].
• They further suggest that although protein kinase C is capable of stimulating the gene by itself, it plays a minimal role in mediating the PTH induction of bone sialoprotein [17].
• We demonstrated that c-Src co-immunoprecipitates with gelsolin, and that osteopontin stimulates its activity [3].

Analytical, diagnostic and therapeutic context of LOC395210

• Three 32P-labeled peptides were isolated by reverse-phase high performance liquid chromatography of thrombin-digested, 32P-labeled OPN [8].
• In addition, immunocytochemistry of type I collagen (COLI) and bone sialoprotein (BSP) suggests that inhibition of NCX by 1.0 microM KB-R7943 also may impair the secretion of bone matrix proteins by the osteoblasts [18].
• The effect of osteopontin was mimicked by RGD containing peptides and blocked by a avb3 antibody, demonstrating that signals generated by integrin ligation contributed to the actions of osteopontin [14].
• Osteocalcin and osteopontin were characterized by several criteria (electrophoresis, immunoblotting, chromatographic characteristics, and response to 1,25(OH)2D3) which confirmed their molecular properties as being identical to osteoblast synthesized proteins [19].
• Osteopontin mRNA expression was examined using reverse transcription-polymerase chain reaction (RT-PCR) of total RNA from vascular tissues with specific primers constructed on the basis of the reported fowl osteopontin nucleotide sequence [20].

References