Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Osteonectin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources

Different bone integration profiles of turned and acid-etched implants associated with modulated expression of extracellular matrix genes.

PURPOSE: The manner in which surface roughness of Implants affects bone-implant integration remains unknown. This study correlated morphologic profiles of bone-implant integration and extracellular matrix (ECM) gene expression in response to the placement of implants with different surface topographies. MATERIALS AND METHODS: T-shaped hollow implants with turned and dual acid-etched (DE) surfaces were placed into rat femurs. A bone integration curve (BIC) was created from serial histomorphometric measurements within the implant chamber. The mRNA expression pattern of ECM genes in bone healing with or without implants was examined using reverse transcriptase-polymerase chain reaction. RESULTS: At week 2, the BIC of the DE implant increased near the implant surface, whereas that of the turned implant decreased. The bone-to-implant contact rate of the DE Implant was 6- and 2.5-fold higher than that of the tuned Implant at weeks 2 and 4, respectively. A spatially standardized histomorphometry revealed that, at week 2, the DE implant had a greater bone volume than the turned implant in a zone near the implant, but not in zones distant from the implant surface. The DE implant evoked an accelerated mRNA expression for osteonectin and osteocalcin compared with the turned Implant, along with an up-regulated expression for bone sialoprotein II, collagen III, and integrins in initial healing stages up to week 1. DISCUSSION AND CONCLUSION: The results indicate that different histologic bone integration profiles associated with increased surface roughness may be explained, in part, by the modulated expression of the selected ECM-related genes. The data provide evidence supporting the fact that gene regulation occurs at local levels of implant surfaces in vivo.

Analysis of Variance↗

Markers of complement-dependent and complement-independent glomerular visceral epithelial cell injury in vivo. Expression of antiadhesive proteins and cytoskeletal changes.

BACKGROUND: Visceral glomerular epithelial cells (GEC) are an important component of the glomerular filtration barrier to proteins. While ultrastructural GEC changes have frequently been observed in proteinuric states, no suitable light microscopic markers of GEC injury have yet been identified. EXPERIMENTAL DESIGN: We have analyzed in vivo the GEC expression of proteins known to be involved in cell shape changes. SPARC (osteonectin, BM-40) and tenascin (cytotactin, J1, hexabrachion) belong to a group of anti-adhesive glycoproteins, that modulate cell-matrix interactions. We also studied cytoskeletal intermediate filament proteins, including desmin and vimentin. The GEC expression of SPARC, tenascin, desmin, and vimentin was analyzed in various types of GEC injury in the rat, including complement-mediated injury (passive Heymann nephritis, autologous immune complex nephritis, conA anti-conA nephritis), complement-independent injury (nephrotoxic nephritis), toxic injury (aminonucleoside nephrosis) and hypertensive injury (5/6 nephrectomy, angiotensin-II infusion). A complement-mediated model of mesangial cell injury (anti-Thy 1.1 mesangial proliferative nephritis) served as a control. RESULTS: SPARC mRNA and protein were constitutively expressed in normal rat glomeruli. Immunostaining and immunoelectron microscopy primarily localized SPARC to the cytoplasm of GEC. Markedly increased glomerular SPARC synthesis and GEC immunostaining was observed in all instances of complement-mediated GEC injury but in none of the other conditions. In contrast, glomerular immunostaining for tenascin, that also stained in a GEC pattern, either remained unchanged or increased to a minor degree (complement-mediated models). GEC immunostaining for desmin in normal rats was low and variable, and increased significantly in any form of GEC injury but not in anti-Thy 1.1 nephritis. No concomitant increase of GEC immunostaining for vimentin was detectable, which could have been due to the constitutively high expression of vimentin in GEC. CONCLUSIONS: SPARC and desmin, but not tenascin or vimentin, are suitable light microscopic markers of GEC injury. The combined staining for these proteins may be useful in differentiating the mechanisms of GEC injury.

Animals↗

Calcification of human valve interstitial cells is dependent on alkaline phosphatase activity.

BACKGROUND AND AIM OF THE STUDY: The calcification of heart valves is associated with valve degeneration and failure, but the mechanisms involved are poorly understood. The presence of lamellar bone has been demonstrated in calcified aortic valves. Since osseous calcification is closely associated with alkaline phosphatase (ALP) activity, it was hypothesized that ALP activity might be implicated in the calcification of isolated leaflet interstitial cells (ICs). METHODS: Human valve leaflet ICs were isolated from transplant-explanted hearts at the time of transplantation (n = 12). RESULTS: Isolated leaflet ICs expressed the fibroblast-specific antigen (100% of cells) and smooth muscle (SM) alpha-actin (70-80% of cells), but osteoblastic markers were not expressed. Cultured ICs did not calcify spontaneously, however when the growth medium was supplemented with beta-glycerophosphate (an organic phosphate) it induced the formation of calcified nodules that expressed osteonectin and ALP, but not SM alpha-actin. Beta-glycerophosphate-induced calcification of ICs showed a time-dependent effect on the calcium content of treated cells over a 14-day period. ALP activity was considerably increased in beta-glycerophosphate-treated ICs, and this correlated with the calcium content (r = 0.5: p = 0.01). Levamisol (an ALP inhibitor) inhibited the beta-glycerophosphate-induced calcification process, as well as the expression of osteoblastic differentiation markers. CONCLUSION: Isolated and cultured leaflet ICs did not calcify spontaneously, though organic phosphate induced the formation of calcified nodules that expressed osteoblastic markers. The calcification of isolated ICs was seen to be dependent on ALP activity.

Actins↗

Expression of SPARC in tongue carcinoma of stage II is associated with poor prognosis: an immunohistochemical study of 86 cases.

SPARC (secretory protein acidic and rich in cysteine), also known as osteonectin or BM-40, associates with progression in various kinds of tumors. We have examined whether SPARC expression can be a prognostic marker for patients with head and neck squamous cell carcinomas (HN-SCC). We examined immunolocalization of SPARC in 86 clinical specimens of tongue carcinoma. Although there was no correlation between SPARC positivity in the tumor cells and tumor stages, the 5-year overall survival rate was significantly lower in the SPARC positive cases (28.6%) than in the SPARC negative cases (91.7%), confined to stage II patients (p < 0.001, Wilcoxon test). Additionally, in stage II cases (n = 3), frequency of the postoperative metastasis was significantly higher in SPARC positive cases (5/8, 62.5%) than in the negative cases (1/15, 6.7%) (p < 0.01, chi2 test). Together with these results, SPARC can be a beneficial prognostic marker for the stage II tongue carcinoma, of which clinical outcomes are sometimes difficult to predict.

Female↗

[Expression of mineral-associated markers in human dental follicle cells in vitro].

OBJECTIVE: To culture human dental follicle cells in vitro and observe their mineralization characteristics. METHODS: Human dental follicle tissues were digested with bacterial collagenase and cultured to obtain dental follicle cells. Mineralization characteristics of these cells were identified by immunohistochemistry and reverse transcription (RT)-PCR. Dental follicle cells were incubated with mineralization-inducing agents to observe the formation of mineralized nodules. RESULTS: Immunohistochemistry staining revealed expressions of type I collagen, type III collagen, osteopontin and osteonectin in the cytoplasm of dental follicle cells cultured in vitro. Low levels of bone sialoprotein, osteocalcin and alkaline phosphatase mRNA were also detected by RT-PCR. Mineralized nodules were observed after 20 days of incubation with mineralization-inducing agents with positivity for von-Kossa staining. CONCLUSION: Human dental follicle cells cultured in vitro show some features of osteoblasts or cementoblasts and can be used as the seed cells for periodontal tissue engineering.

Calcification, Physiologic↗

Human bone cells in vitro.

Human bone cell cultures were established by maintaining collagenase-treated bone fragments in low Ca++ medium. The resulting cell cultures exhibited a high level of alkaline phosphatase activity and produced a significant increase in intracellular cAMP when exposed to the 1-34 fragment of human parathyroid hormone. With continued culture, the cells formed a thick, extracellular matrix that mineralized when cultures were provided daily with normal levels of calcium, fresh ascorbic acid (50 micrograms/ml) and 10 mM beta-glycerol phosphate. Biosynthetically, these cells produced type I collagen (without any type III collagen), and the bone-specific protein, osteonectin. In addition, the cells produced sulfated macromolecules electrophoretically identical to those positively identified as the bone proteoglycan in parallel cultures of fetal bovine bone cells. This technique provides a useful system for the study of osteoblast metabolism in vitro.

Adolescent↗

Characterization of the mouse SPARC/osteonectin gene. Intron/exon organization and an unusual promoter region.

Two overlapping cosmids have been isolated containing the entire murine gene for SPARC (osteonectin), a Ca2+-binding, phosphorylated glycoprotein associated with extracellular matrix synthesis and remodeling. The gene contains 10 exons and covers 26.5 kilobase pairs of DNA. Exon analysis shows that the two N-terminal glutamic acid-rich sequences which are predicted to undergo conformational change upon binding of calcium, as well as the C-terminal EF-hand Ca2+-binding domain are each encoded by a single exon. Comparative analysis of the exon sequence does not support the idea that the SPARC gene has evolved by shuffling of exons from other Ca2+-binding proteins. The 5' flanking region of the SPARC gene, which promotes transcription when placed in front of the bacterial chloramphenicol acetyltransferase gene, contains neither "TATA" nor "CAAT" box sequences. However, unlike most other genes lacking these motifs, mapping of the 5' end of the SPARC gene by RNase protection and primer extension analysis reveals only a single major and one minor transcription start site. The upstream region to -120 includes six repeats of the sequence GGAGG, two repeats of the sequence 5' GGAGG A/C GGAGGG 3', and a potential transcription factor AP-2 binding site.

Acetyltransferases↗

Effect of growth factors on bone cell replication and differentiation.

Bone formation is a process regulated by effects on bone cell replication and on differentiated function, which is primarily represented by changes in bone collagen synthesis. The effects of hormones on bone formation have been reviewed extensively, and this article describes the effects of systemic and local growth factors. Systemic growth factors, such as epidermal growth factor and fibroblast growth factor, stimulate cell replication in skeletal and nonskeletal tissues but inhibit differentiated function; platelet-derived growth factor stimulates cell replication and generalized protein synthesis by differentiated cells. The only systemic factor that simultaneously stimulates bone cell replication and differentiation is insulinlike growth factor, or somatomedin. The growth of skeletal and nonskeletal tissues also appears to be regulated by locally synthesized factors. Bone contains an autologous bone-derived growth factor that stimulates bone collagen and DNA synthesis, while cartilage contains a somatomedinlike peptide that stimulates cartilage growth. Other noncollagenous bone proteins, such as osteonectin and osteocalcin, might have a role in mineralization, but, as yet, they have not been reported to have a definite effect on bone formation. Bone also contains prostaglandins and local regulators of bone resorption, while the macrophage, an osteoclast-related cell, releases peptides that stimulate bone formation in vitro. In conclusion, bone formation is a complex process regulated not only by hormones but also by systemic and local growth factors.

Animals↗

Pericyte differentiation.

Pericytes are defined in vivo by their location: They are embedded within the basement membrane of microvessels. They form an integral part of the microvascular wall and are believed to participate in angiogenesis, although their precise role is not clear. Pericytes derived from the retinal microvasculature have been cultured and identified by a series of phenotypic characteristics that clearly distinguishes them from other stromal cells such as smooth muscle cells. Pericytes in vitro form multicellular nodules rich in extracellular matrix. This matrix becomes mineralized in the presence of growth medium containing serum, without exogenous beta-glycerophosphate. These results indicate that pericytes represent primitive mesenchymal cells able to differentiate into an osteogenic phenotype. Pericyte differentiation also is defined by alterations in their response to transforming growth factor beta 1 and changes in the synthesis and/or deposition of various extracellular matrix proteins such as laminin, Type IV collagen, tenascin, Type X collagen osteonectin, and thrombospondin-1. Angiogenesis is associated commonly with mineralization. These data suggest that pericytes may contribute to mineralization in vivo.

Animals↗

Expression of bone matrix protein messenger ribonucleic acids in human breast cancers. Possible involvement of osteopontin in development of calcifying foci.

BACKGROUND: Development of calcifying foci is a fairly common finding in human breast cancers, and the deposition of calcium phosphate is observed in such foci. The calcium phosphate is a physiologic component of bones and teeth. Since the expression of messenger (m) RNAs of osteopontin (OPN), osteocalcin (OC), osteonectin (ON), and matrix gla protein (MGP) has been described in bones and teeth, we examined the mRNA expression of OPN, OC, ON, or MGP in the calcifying foci that were observed in human breast cancers. EXPERIMENTAL DESIGN: Cell types expressing mRNAs of OPN, ON or MGP were identified with combination of in situ hybridization and immunohistochemistry. RESULTS: The OPN mRNA-expressing cells clustered around the necrotic foci within cancer cell nests, and the examination with anti-OPN antibody revealed that OPN protein was localized in such necrotic foci where calcium phosphate deposited. The OPN mRNA-expressing cells were identified as macrophages by staining the adjacent section with the anti-CD68 PG-M1 monoclonal antibody which specifically recognizes macrophages. Neither ON mRNA-expressing cells nor MGP mRNA-expressing cells appeared to correlate with the deposition of calcium phosphate. CONCLUSIONS: The OPN protein produced by macrophages appeared to play a significant role for development of calcifying foci within necrotic area of breast cancers.

Antibodies, Monoclonal↗

Transient expression of SPARC in the dorsal axis of early Xenopus embryos: correlation with calcium-dependent adhesion and electrical coupling.

Our comprehension of the molecular mechanisms underlying embryogenesis has been greatly enhanced by the identification and characterization of associated extracellular matrix macromolecules. Using Xenopus laevis as a model, we investigated the expression and distribution of SPARC (Secreted Protein, Acidic, Rich in Cysteine; also called osteonectin and BM-40) during early embryonic development. SPARC has been found to be enriched in tissues undergoing rapid morphological development, differentiation, and remodeling. In Xenopus, SPARC transcripts are first expressed by primordial cells which give rise to the first embryonic tissues, the notochord and somites. SPARC RNA levels remained high throughout the rapid morphological development and differentiation phase of these tissues, and then rapidly decreased. Of particular interest, SPARC protein began to accumulate within the intersomitic clefts at the onset of trunk myotome contraction. The intersomitic enrichment of SPARC remained high as long as the myotomes remained electrically coupled, principally by gap junctions. As myotomes became innervated, SPARC expression decreased dramatically within the somites. SPARC was also found to be enriched within other tissues, such as the neural tube and epidermis. In addition, the selective spatial-temporal enrichment of SPARC suggests it makes important calcium-dependent contributions to early morphological development.

Animals↗

Expression of SPARC in normal and fibrotic livers.

SPARC (secreted protein, acidic and rich in cysteine)--also known as osteonectin, BM-40, and 43K glycoprotein--is secreted by endothelial cells and fibroblasts in response to culture shock. SPARC has been found in association with tissues undergoing cell proliferation, migration, and extracellular matrix remodeling. We demonstrate that normal livers from humans, rats, and mice express substantial levels of SPARC messenger RNA (mRNA). Moreover, when compared with control specimens, significantly increased levels of SPARC mRNA were found in fibrotic livers from two animal models of liver disease: murine schistosomiasis and carbon tetrachloride-induced fibrosis in rats. Fibrotic human livers also had markedly increased levels of SPARC mRNA in comparison with normal livers. We also detected an increased production of SPARC protein in the liver of animals treated with carbon tetrachloride. By immunocytochemical analysis, SPARC protein was apparent in freshly isolated Ito cells. Hybridization studies showed Ito cells to be the main source of SPARC mRNA. Extracts from a Kupffer-endothelial cell fraction exhibited traces of SPARC transcript, but expression of SPARC mRNA was absent in extracts from freshly isolated hepatocytes. These studies demonstrate the increased expression of SPARC--a protein that modulates cell shape and disrupts cell-matrix interactions--during the initial stages of hepatic fibrosis.

Animals↗

SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells.

SPARC, also termed osteonectin, BM-40 and 43K protein, is an acidic, cysteine-rich component of the extracellular matrix that has been shown to be directly regulated by progesterone and dexamethasone and indirectly by cytokines. By RNA fingerprinting technique, we cloned a SPARC homolog from the normal human ovarian surface epithelial (HOSE) cells and demonstrated that it is expressed at high levels in the normal HOSE cells but at much lower levels in ovarian carcinoma cells in vitro and in vivo. Subsequently, we transfected the full length SPARC cDNA into an ovarian carcinoma cell line SKOV3 and showed that it reduced the growth rate of the cancer cell line in culture and reduced the cell's ability to induce tumours in nude mice. These results suggest that SPARC may play an important role in growth and and differentiation of the HOSE cells and support the hypothesis that SPARC functions as a tumor suppressor.

Animals↗

In vivo implantation of human osteosarcoma cells in nude mice induces bones with human-derived osteoblasts and mouse-derived osteocytes.

Two human osteosarcoma cell lines, Hu09 and OST, were suspended in Matrigel (Becton Dickinson Labware, Bedford, Massachusetts) and implanted subcutaneously in the backs of nude mice. To study phenotypic changes of tumor cells and host cells, expression of mRNA for osteopontin (OPN), osteocalcin (OC), and osteonectin (ON) was analyzed by in situ hybridization. Bone tissue was formed in the tumors derived from Hu09 cells. OPN mRNA was transcribed predominantly in osteocyte-like cells within the bone, whereas OC mRNA was transcribed in osteoblast-like cells that surrounded the bone. ON mRNA was detected in both types of cells. The similarity of the expression pattern of OPN, OC, and ON during osteogenesis of Hu09 cells to that of normal skeletal development suggests that the bone formed in Hu09-implanted mice is the same as normal bone tissue. By DNA-DNA in situ hybridization using a human-specific Alu probe and a mouse-specific m-L1 probe, osteoblast-like cells in Hu09 tumorous bone were, however, of human origin, whereas osteocyte-like cells were of mouse origin. In the tumors derived from OST cells, no osteogenesis was observed during the experimental period, and the expression of OPN, OC, and ON was not detected in tumor cells. An endochondral bone formation was not evident when these cells were simply implanted into muscle tissue. An endochondral bone was, however, reactively induced in the host mUscle tissue either when 1 alpha-hydroxyvitamin D3 and all-transretinoic acid were administered to OST-implanted mice or when Hu09 cells were pretreated with dexamethasone before implantation. Hu09 implantation seems to be a useful tool not only for the study of the differentiation of osteosarcoma cells but also for the investigation of the mechanism of bone formation. This system, using Hu09 and OST, may provide us with a new tool for the isolation of the unidentified factors that induce or inhibit osteogenesis in vivo.

Animals↗

Age-related changes in bone formation, osteoblastic cell proliferation, and differentiation during postnatal osteogenesis in human calvaria.

We have determined the age-related changes in the growth characteristics and expression of the osteoblast phenotype in human calvaria osteoblastic cells in relation with histologic indices of bone formation during postnatal calvaria osteogenesis. Histomorphometric analysis of normal calvaria samples obtained from 36 children, aged 3 to 18 months, showed an age-related decrease in the extent of bone surface covered with osteoblasts and newly synthesized collagen, demonstrating a progressive decline in bone formation during postnatal calvaria osteogenesis. Immunohistochemical analysis showed expression of type I collagen, bone sialoprotein, and osteonectin in the matrix and osteoblasts, with no apparent age-related change during postnatal calvaria osteogenesis. Cells isolated from human calvaria displayed characteristics of the osteoblast phenotype including alkaline phosphatase (ALP) activity, osteocalcin (OC) production, expression of bone matrix proteins, and responsiveness to calciotropic hormones. The growth of human calvaria osteoblastic cells was high at 3 months of age and decreased with age, as assessed by (3H)-thymidine incorporation into DNA. Thus, the age-related decrease in bone formation is associated with a decline in osteoblastic cell proliferation during human calvaria osteogenesis. In contrast, ALP activity and OC production increased with age in basal conditions and in response to 1,25(OH)2 vitamin D3, suggesting a reciprocal relationship between cell growth and expression of phenotypic markers during human postnatal osteogenesis. Finally, we found that human calvaria osteoblastic cells isolated from young individuals with high bone formation activity in vivo and high growth potential in vitro had the ability to form calcified nodular bone-like structures in vitro in the presence of ascorbic acid and beta-glycerophosphate, providing a new model to study human osteogenesis in vitro.

Age Factors↗

Fibrous dysplasia of bone in the McCune-Albright syndrome: abnormalities in bone formation.

In addition to café-au-lait pigmentation patterns and hyperendocrinopathies, fibrous dysplasia of bone is a major finding in the McCune-Albright syndrome. Activating missense mutations of the Gs alpha gene leading to overactivity of adenylyl cyclase have been identified in patients with McCune-Albright syndrome, but the mechanism leading to the specific development of fibrous dysplasia in bone has not been elucidated. By means of specific peptide antisera and reverse transcriptase polymerase chain reaction in situ hybridization, we show that expression of Gs alpha and its mRNA is critically up-regulated during maturation of precursor osteogenic cells to normal osteoblast cells and that this pattern of expression is retained in fibrous dysplasia. A functional characterization of fibrous dysplastic tissues revealed that the fibrotic areas consist, in fact, of an excess of cells with phenotypic features of pre-osteogenic cells, whereas the lesional bone formed de novo within fibrotic areas represents the biosynthetic output of mature but abnormal osteoblasts. These cells are noted for peculiar changes in cell shape and interaction with matrix, which were mimicked in vitro by the effects of excess exogenous cAMP on human osteogenic cells. Osteoblasts involved with the de novo deposition of lesional bone in fibrous dysplasia produce a bone matrix enriched in certain anti-adhesion molecules (versican and osteonectin), and poor in the pro-adhesive molecules osteopontin and bone sialoprotein, which is in contrast to the high levels of these two proteins found in normal de novo bone. Our data indicate the need to reinterpret fibrous dysplasia of bone as a disease of cells in the osteogenic lineage, related to the effects of excess cAMP on bone cell function. They further suggest that a critical, physiological, maturation-related regulation of Gs alpha levels makes cells in the osteogenic lineage a natural target for the effects of mutations in the Gs alpha gene and may provide a clue as to why bone itself is affected in this somatic, mutation-dependent disease.

Adolescent↗

Elastic fiber during development and aging.

Elastin molecules aggregate in the extracellular space where they are crosslinked by stable desmosine bridges. The resulting polymer is structurally organized as branched fibers and lamellae, which, in skin, are wider (a few microns) in the deep dermis and become progressively thinner (fraction of a micron) towards the papillary dermis. Several general and local factors seem to regulate elastin gene expression, deposition and degradation. In skin, the volume density of the elastin network increases from birth up to maturity, when it accounts for about 3-4% of the tissue. However, its amount and distribution depend on dermis areas, which are different among subjects and change with age. Several matrix molecules (glycosaminoglycans, decorin, biglycan, osteopontin) have been found to be associated with elastin into the normal fiber, and several others have been recognized within pathologic elastic fiber (osteonectin, vitronectin, alkaline phosphatase in PXE). With age, and in some pathologic conditions, skin elastin may undergo irreversible structural and compositional changes, which seem to progress from localized deposition of osmiophilic materials to the substitution of the great majority of the amorphous elastin with interwoven filaments negative for elastin specific antibodies.

Adult↗

In vitro reactions of human osteoblasts in culture with zirconia and alumina ceramics.

The biocompatibility of two implantable materials, zirconia and alumina ceramics, was investigated in vitro using human osteoblast cell cultures. The viability of osteoblast cells with the materials was evaluated by the methylthiazole sulfate test that revealed an absence of any cytostatic or cytotoxic effect. Cell proliferation kinetic and total protein synthesis in osteoblasts with zirconia or alumina were similar to that observed in control cells cultured on glass coverslips. Light and scanning electron microscopic examinations showed an intimate contact between osteoblasts and the substrates; well-spread cells were observed on the surfaces of both materials. Adhesion ability and morphological characteristics were preserved in osteoblast cultures with these substrates. Moreover, immunohistochemical staining in osteoblasts with zirconia and alumina showed the capacity of these cells to elaborate the extracellular matrix composed of types I and V collagen, osteocalcin, osteonectin, bone sialoprotein, and cellular fibronectin. Finally, DNA image cytometry and interphase silver-nucleolar organizer regions quantification were applied as complementary biocompatibility tests to detect any changes in DNA synthesis and cell proliferation, respectively. The results showed that neither material altered cell ploidy or cell growth rate in accordance with the absence of any inducing effect on DNA synthesis or proliferation.

Aluminum Oxide↗