Disease relevance of SPP1

• The association of the SPP1 marker with birth weight (P < 0.006), weaning weight (P < 0.007), and yearling weight (P < 0.003) was consistent with the previously reported effects of SPP1 genotype on yearling weight [1].
• We conclude therefore, that the inhibitory potency of the bone sialoprotein-derived peptides on breast cancer cell adhesion to bone is not solely due to a properly positioned RGD-motif alone but is also determined by its flanking regions, together with the tertiary structure of the EPRGDNYR peptide [2].
• Osteopontin (OPN) is a highly modified protein that is found in many tissues and has been associated with a variety of physiological and pathological processes [3].
• Bone OPN is a potent inhibitor of hydroxyapatite crystal formation and stimulates bone resorption by osteoclasts; these activities, as well as others, are dependent upon phosphorylation of the protein [3].
• While the protein substrates to which OPN is linked in vivo have not been identified, it is reasonable to speculate that this capacity of OPN may dictate its extracellular location and thereby affect its role in bone homeostasis, tumorigenesis, metastasis, resistance to bacterial infections or, perhaps, wound repair [4].

High impact information on SPP1

• For one QTL on bovine chromosome 6 (BTA6), previously fine-mapped to a 420-Kb region, mutations in two different genes (OPN and ABCG2) have been proposed as the underlying functional mutation [5].
• Both control PC12 cells and PC12-tet cells injected into nude mice produced tumors containing bone material, as evidenced by von Kossa staining for calcium and immunostaining with bone sialoprotein and alkaline phosphatase antiserum [6].
• The cells were identified as functional osteoblasts by indirect immunofluorescence using antibodies against three bone-specific, noncollagenous matrix proteins (osteonectin, the bone proteoglycan, and the bone sialoprotein) and against type 1 collagen [7].
• In separate experiments, confluent cultures of the cells were radiolabeled and shown to synthesize and secrete osteonectin, the bone proteoglycan and the bone sialoprotein by immunoprecipitation and fluorography of SDS polyacrylamide gels [7].
• Exogenously added bone sialoprotein peptides with this amino acid sequence in their backbone structure, but not the more common fibronectin-derived GRGDS peptide, strongly inhibited breast cancer cell adhesion to extracellular bone matrix at micromolar concentrations [2].

Biological context of SPP1

• Phosphorylation of purified bovine bone sialoprotein and osteopontin by protein kinases [8].
• Phenotypic records for this population included twinning rate and ovulation rate, providing an opportunity to examine the potential effects of SPP1 genotype on reproductive traits [1].
• Association of a single nucleotide polymorphism in SPP1 with growth traits and twinning in a cattle population selected for twinning rate [1].
• In the current investigation we report the genomic organization of the SPP1 gene, which comprises seven exons, six of which contain coding sequence [9].
• A highly informative short tandem repeat polymorphism isolated at the SPP1 locus showed no recombination with the autosomal dominant disorder dentinogenesis imperfecta type II [9].

Anatomical context of SPP1

• The large number of covalently bound phosphates on the extracellular phosphoproteins osteopontin (OPN) and bone sialoprotein (BSP) have been implicated in biological functions such as mineral deposition and osteoclast binding [8].
• Osteopontin (SPP1) is the principal phosphorylated glycoprotein of bone that is also expressed in a limited number of other tissues including dentine [9].
• Chondrocytes, which had been maintained in suspension culture, attached to fibronectin, bone sialoprotein, collagen II, and two novel 36- and 58-kDa proteins isolated from cartilage [10].
• When the soluble digests were chromatographed on DEAE-cellulose, the elution profiles indicated the presence in each tissue of a variety of glycoproteins and a proteoglycan fraction, and showed clearly that an acidic glycoprotein corresponding to bone sialoprotein was not present in tendon [11].
• We concluded that the primary sources of OPN in bull SP are the seminal vesicles and ampulla [12].

Associations of SPP1 with chemical compounds

• Osteopontin (OPN) is a multiphosphorylated glycoprotein found in bone and other normal and malignant tissues, as well as in the physiological fluids urine and milk [13].
• These data collectively demonstrate that dual alpha(4)beta(1) integrin binding sites are present in a 38 amino acid domain within the N-terminal thrombin fragment of OPN [14].
• Attachment to fibronectin and bone sialoprotein was inhibited by competition with an Arg-Gly-Asp containing peptide, whereas attachment to the 36- and the 58-kDa proteins was not affected [10].
• OPN was not detected immunohistochemically in epididymal, ampullary, or ejaculated sperm treated with or without Triton X-100 [12].
• In EDTA extracts of long bones, the majority of the radiolabel was demonstrated to be associated with intact OPN [15].

Other interactions of SPP1

• There was no markedly enhanced mRNA expression of bone sialoprotein (BSP) and glyceraldehyde-3-phosphate dehydrogenase compared with that of control [16].

Analytical, diagnostic and therapeutic context of SPP1

• Molecular cloning and sequence analysis of cDNA for a 59 kD bone sialoprotein of the rat: demonstration that it is a counterpart of human alpha 2-HS glycoprotein and bovine fetuin [17].
• Sequence alignment revealed that these glutamines are conserved in all known OPN sequences, indicating a functional importance of this region of the protein [18].
• N-terminal sequence analysis of the pure protein yielded a 15-amino acid sequence (VKPXSSGXSEEKQLN) that was 86% homologous to bovine osteopontin-k precursor [19].
• Immunofluorescence histochemistry localized OPN in the lumen and epithelial cells of the seminal vesicle and ampulla, but not in tissues of testis, epididymis, prostate, and bulbourethral gland [12].
• Antisera generated against human recombinant OPN, as well as antiserum prepared against purified bovine seminal plasma OPN, reacted with protein in SP, accessory sex gland fluid, seminal vesicle fluid, ampullary fluid, and urine using one- and two-dimensional SDS-PAGE Western blot analysis [12].

References