Osteopontin, a protein that is
produced by osteoblasts under stimulation by calcitriol and binds tightly to hydroxyapatite, was shown by Reinholt et
al. (1990) to be involved in the anchoring of osteoclasts to the mineral of bone matrix. Vitronectin receptor ,
which has specificity for osteopontin, is preferentially located in the area of the osteoclast plasma membrane involved
in the binding process. The
osteopontin receptor CD44 has been targeted by diverse therapeutic strategies,
including cytotoxic and immunotherapeutic approaches. The receptor integrin
alpha(V)beta(3) contributes not only to tumor cell dissemination, but also to
angiogenesis and osteolysis in bone metastases.
NCBI Summary:
The protein encoded by this gene is involved in the attachment of osteoclasts to the mineralized bone matrix. The encoded protein is secreted and binds hydroxyapatite with high affinity. The osteoclast vitronectin receptor is found in the cell membrane and may be involved in the binding to this protein. This protein is also a cytokine that upregulates expression of interferon-gamma and interleukin-12. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
General function
Ligand, Cytokine, Growth factor
Comment
Cellular localization
Secreted
Comment
Comparison of Serum Adiponectin and Osteopontin Levels along with Metabolic Risk Factors Between Obese and Lean women with and without PCOS. Alatas SE et al. (2020) To investigate the possible relation between serum adiponectin and osteopontin levels as metabolic risk markers among women with different PCOS phenotypes Material and Methods: In an University Hospital setting PCOS patients diagnosed according to Rotterdam Consensus Conference criteria, excluded of other endocrinopathies, and having spontaneous menarche and normal sexual development, and with BMI between 18 and 35 were recruited. Overall, 57 PCOS patients and age and BMI matched 57 healthy controls were included to the study. LF/FSH ration, FAI, and DHEAS-S was found to be significantly higher in women with PCOS. There was significant interaction between PCOS status and obesity for serum adiponectin levels. Although mean adiponectin and osteopontin levels were similar among cases and controls, a further two-way ANOVA comparison within lean and obese subgroups revealed adiponectin to be significantly lower in lean PCOS women than lean controls. LH/FSH ratio and adiponectin levels were all found to differ between lean counterparts, however they did not show any corelation with metabolic markers (cholesterol panel, HOMA or CRP levels) neither in overall lean women nor in lean PCOS subgroup. Serum adiponectin levels in lean PCOS women are significantly lower than that of in lean controls. On the other hand mean adiponectin and osteopontin levels were similar between PCOS cases and controls overall. There is a need for prospective data regarding the clinical value of adiponectin investigating it as a long-term metabolic risk factor in lean cases.//////////////////
Polycystic Ovary Syndrome is Associated with Increased Osteopontin Levels. Saklamaz A et al. (2015) Osteopontin (OPN) is a multi-functional secreted glycoprotein that plays a crucial role in glucose metabolism and inflammatory process. Growing evidence suggests that there is a link between OPN and ovarian function. However, no such link has yet been found for OPN in polycystic ovary syndrome (PCOS). Our aim was to ascertain whether circulating OPN levels are altered in women with PCOS and to determine whether OPN levels differ between the follicular phase and mid-cycle of the menstrual cycle in eumenorrheic women. 150 women with PCOS and 150 age- and BMI-matched controls without PCOS were recruited for this prospective observational study. OPN levels were measured using ELISA. Metabolic parameters were also determined. Circulating OPN levels were significantly elevated in PCOS women compared with controls (69.12 ± 31.59 vs. 42.66 ± 21.28 ng/ml, P<0.001). OPN levels were significantly higher at mid-cycle than in the follicular phase in eumenorrheic women. OPN was positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free-testosterone and high sensitivity C-reactive protein (hs-CRP). Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 3.64 for patients in the highest quartile of OPN compared with those in the lowest quartile (OR=3.64, 95% CI=2.42-5.57, P=0.011). Our findings indicate that BMI, HOMA-IR, hs-CRP and free-testosterone are independent factors influencing serum OPN levels and that OPN is an independent predictor for HOMA-IR. PCOS is associated with increased OPN levels.//////////////////
Ovarian function
Steroid metabolism
Comment
Gonadotropin regulation and role of ovarian osteopontin in the periovulatory period. Kuwabara Y et al. (2014) Osteopontin (OPN), a secreted glycoprotein, has multiple physiological functions. This study investigated the regulation and roles of OPN in the mouse ovary during the periovulatory stages. Immature female mice were treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to simulate follicle maturation and ovulation. In situ hybridization and real-time RT-PCR were performed to assess expression of Opn in the periovulatory ovary. Granulosa cells (GCs) from PMSG-primed immature mice were cultured with or without hCG in the presence or absence of OPN, and effects on expression of Opn, progesterone synthesis, and vascular endothelial growth factor (VEGF) signaling were assessed by real-time RT-PCR, ELISA, and western blotting analysis. Opn transcripts were significantly upregulated 3 h after hCG treatment, followed by a peak at 16 h, and the transcripts localized to GCs. Incubation with hCG significantly increased quantities of Opn transcripts in GCs and OPN levels in the culture medium at 12 and 24 h. Furthermore, OPN treatment caused a significant increase in the levels of Star protein, P 450 cholesterol side-chain cleavage enzyme (p450scc), 3-beta-hydroxysteroid dehydrogenase (Hsd3b), and progesterone in the culture medium. OPN treatment promoted Vegf expression in GCs, which was significantly suppressed by a phosphoinositide 3-kinase (PI3K) inhibitor. In addition, OPN treatment stimulated phosphorylation of AKT, a downstream PI3K signaling molecule. In conclusion, expression of Opn was upregulated in mouse ovarian GCs in response to a gonadotropin surge through epidermal growth factor receptor signaling, which enhances progesterone synthesis and Vegf expression during the early-luteal phase.//////////////////
Osteopontin is expressed in the oviduct and promotes fertilization and preimplantation embryo development of mouse. Liu Q 2014 et al.
Summary Osteopontin (OPN) is a multifunctional phosphoprotein that is detected in various tissues, including male and female reproductive tracts. In this study, we evaluated OPN expression in mouse oviducts during the estrus cycle, and at days 1-5 of pregnancy and pseudopregnancy by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The mice oocytes, sperm and embryos were treated with different concentrations of anti-OPN antibody in vitro to detect the function of OPN in fertilization and preimplantation embryo development. OPN mRNA and protein expression in mouse oviducts were cyclic dependent throughout the estrous cycle, which was highest at estrous and lowest at diestrous. Such a phenomenon was consistent with the change in estrogen level in mice. The expression levels of OPN in mice oviduct of normal pregnancy and pseudopregnancy were significantly different, which indicated that OPN expression in mouse oviducts was depend on estrogen and preimplantation embryo. Furthermore, anti-OPN antibody treatment could reduce the rates of fertilization, cleavage and blastocyst formation in vitro in a dose-dependent way. Overall, our results indicated that the expression of OPN in mouse oviducts during the estrous cycle and early pregnancy is likely regulated by estrogen and the embryo, and OPN may play a vital role in oocyte fertilization and preimplantation embryo development.
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Expression regulated by
LH, Steroids
Comment
Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.
Ovarian localization
Granulosa, Theca, Luteal cells, ovarian tumor
Comment
Craig AM, et al reported the murine gene encoding secreted phosphoprotein 1
(osteopontin).
The Spp-1 mRNA was localized in several tissues, consistent with
previous reports, and to novel sites in ovary, and in the skin and ventral fatty tissue of
pregnant and lactating mice.
Izhar
Robert A Mastroeni, Deborah M Sindoni, Dana M Banas, Georgius
de Haan, Donald E Frail, Susan L Fitzpatrick reported the identification and Characterization of Osteopontin and
Other Estrogen Regulated Genes in Rat and Mouse Granulosa
Cells In Vivo.Brown LF, et al reported the osteopontin expression and distribution in human carcinomas.
All 14 tumors studied by Northern analysis showed very
substantial increases in OPN messenger (m)RNA when compared to corresponding
normal tissues. Moreover, intense labeling for OPN mRNA was detected in 71 of 76
carcinomas studied by in situ hybridization. In most of the carcinomas studied (colon,
stomach, duodenum, pancreas, breast, lung, bladder, prostate, ovary, thyroid, and
melanoma), tumor cells did not label detectably for OPN mRNA; however,
macrophages intimately associated with tumor cells labeled strongly for the OPN
transcript. Although in most cases tumor cells did not
label detectably for OPN mRNA, both tumor cells and macrophages stained for OPN
protein, suggesting that OPN secreted by macrophages may bind to tumor cells,
possibly through the glycine-arginine-glycine-aspartate-serine cell binding domain in
OPN. Collectively, these data suggest that OPN functions in adhesive interactions at
the tumor/host interface and thereby may influence processes such as invasion and
metastasis.
By the use of Rapid Analysis of Differential Expression, a
type of differential display, genes that were regulated by
17b-estradiol (E2) in vivo (1.5 mg daily for 3 days) were
identified in granulosa cells from immature rats. Fucosidase mRNA
expression was up regulated approximately 5-fold whereas
osteopontin (OPN), osteoprotegerin, and aldehyde dehydrogenase
mRNAs were down regulated approximately 5-fold. These results
were confirmed by Northern blot analysis and/or quantitative
RT-PCR. Brunswig-Spickenheier B, et al 2003 reported the expression of Osteopontin (OPN) mRNA in Bovine Ovarian Follicles and Corpora Lutea.
The matricellular protein osteopontin (OPN) plays a role in various physiological processes, including angiogenesis and tissue remodelling. As these processes are essential for the maintenance of ovarian physiology, the aim of the study was to investigate the expression of OPN (mRNA) in ovarian cells and to evaluate whether it can be regulated by gonadotrophins. Using conventional RT-PCR and real-time PCR, the authors have detected and quantified OPN mRNA as well as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in bovine granulosa, theca and luteal cells. In all cells examined, both genes were found in equal amounts and no striking variations in the expression could be observed between granulosa, theca and luteal cells. Furthermore, no effect on either OPN or GAPDH mRNA expression was evident after culturing ovarian cells in the presence of gonadotrophic hormones, although the cells were still highly responsive in terms of cAMP formation. Although neither variations between different cell types nor a regulation of OPN mRNA expression by gonadotrophic hormones could be detected, the high and unambiguous mRNA expression in steroidogenic cells suggests that OPN should be added to the growing list of intraovarian factors which may be involved in ovarian physiology.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Expression and Regulation of Secreted Phosphoprotein 1 in the Bovine Corpus Luteum and Effects on T Lymphocyte Chemotaxis. Poole D 2013 et al.
Secreted phosphoprotein 1 (SPP1) in the bovine corpus luteum (CL) may regulate cell function during the transitional periods of luteinization and luteal regression. The objectives were to: 1) characterize SPP1 expression in the CL throughout the estrous cycle 2) determine factors that regulate SPP1 expression in luteal cells; and 3) examine the role of SPP1 on lymphocyte chemotaxis, proliferation and function. Secreted phosphoprotein 1 mRNA was greater in fully functional (d10) and late cycle (d18) CL compared to developing (d4) CL. Additionally, SPP1 mRNA increased within 1 hour and remained elevated 4 and 8 hours following induction of luteolysis with prostaglandin (PG)F2a. Expression of the SPP1 receptor, ? integrin, was not different throughout the estrous cycle but decreased following induction of luteolysis. Expression of CD44 increased during the estrous cycle, but did not change during luteal regression. In cultured luteal cells, SPP1 mRNA was upregulated by PGF2a and/or tumor necrosis factor alpha (TNF). Western blots revealed the presence of both full length SPP1 plus multiple cleavage products in cultured luteal cells and luteal tissue. Depletion of endogenous SPP1 did not hinder luteal cell-induced lymphocyte proliferation or lymphocyte phenotype, but did inhibit lymphocyte migration toward luteal cells. Based on these data, it is concluded that SPP1 is initially activated to establish and maintain cellular interactions between steroidogenic and nonsteroidogenic cells during the development of the corpus luteum. Upon induction of luteolysis, SPP1 serves as a signaling molecule to recruit or activate immune cells to facilitate luteal regression and tissue degradation.
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Bobe J, et al reported that a novel osteopontin-like protein is expressed in the trout ovary during ovulation. (thrombin)