[6][7] It is composed of about 300 amino acids (297 in mouse; 314 in human) and is expressed as a 33-kDa nascent protein; there are also functionally important cleavage sites.

[11] All intron-exon boundaries are of the phase 0 type, thus alternative exon splicing maintains the reading frame of the OPN gene.

SPP1 structure corresponds to an osteopontin antibody Full-length OPN (OPN-FL) can be modified by thrombin cleavage, which exposes a cryptic sequence, SVVYGLR on the cleaved form of the protein known as OPN-R (Fig.

It appears an intracellular variant of OPN (iOPN) is involved in a number of cellular processes including migration, fusion and motility.

[23] Osteopontin-c has been suggested to facilitate the anchorage-independent phenotype of some human breast cancer cells due to its inability to associate with the extracellular matrix.

[31] Hypocalcemia and hypophosphatemia (instances that stimulate kidney proximal tubule cells to produce calcitriol (1α,25-dihydroxyvitamin D3)) lead to increases in OPN transcription, translation and secretion.

[38] Stimulation of OPN expression also occurs upon exposure of cells to pro-inflammatory cytokines,[39] classical mediators of acute inflammation (e.g. tumour necrosis factor α [TNFα], infterleukin-1β [IL-1β]), angiotensin II, transforming growth factor β (TGFβ) and parathyroid hormone (PTH),[40][41] although a detailed mechanistic understanding of these regulatory pathways are not yet known.

[47] OPN also has a large number of consensus sequence sites for post-translational phosphorylation of Ser residues to form phosphoserine, providing additional negative charge.

[63][64] In relation to mineralization diseases, the Stenciling Principle is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia and X-linked hypophosphatemia.

[72] The organic part of bone is about 20% of the dry weight, and counts in, other than osteopontin, collagen type I, osteocalcin, osteonectin, and alkaline phosphatase.

OPN serves to initiate the process by which osteoclasts develop their ruffled borders to begin bone resorption.

OPN contains and RGD integrin-binding motif Activated T cells are promoted by IL-12 to differentiate towards the Th1 type, producing cytokines including IL-12 and IFNγ.

[79] In rhesus monkey, OPN prevents macrophages from leaving the accumulation site in brains, indicating an increased level of chemotaxis.

[7] The fact that OPN interacts with multiple cell surface receptors that are ubiquitously expressed makes it an active player in many physiological and pathological processes including wound healing, bone turnover, tumorigenesis, inflammation, ischemia, and immune responses.

Expression of Opn is significantly increased in lung epithelial and subepithelial cells of asthmatic patients in comparison to healthy subjects.

Opn has also a proinflammatory role in TNBS- and dextran sulfate sodium (DSS)-induced colitis, which are mouse models for IBD.

Thus, manipulation of plasma OPN levels may be useful in the treatment of autoimmune diseases, cancer metastasis, osteoporosis and some forms of stress.

Because PDAC secretes alternatively spliced forms of osteopontin, it shows potential for tumor- and disease stage-specific targeting.

Although the exact mechanisms of osteopontin signaling in PDAC are unknown, it binds to CD44 and integrins to trigger processes such as tumor progression and complement inhibition.

[95] AOM1, an anti-osteopontin monoclonal antibody drug developed by Pfizer, Inc. to inhibit osteopontin, showed promise at preventing progression of large metastatic tumors in mouse models of NSCLC.

[96][97] Even though Opn promotes metastasis and can be used as a cancer biomarker, latest studies described novel protecting functions of the molecule on innate cell populations during tumor development.

Particularly, maintenance of a pool of natural killer (NK) cells with optimal immune function is crucial for host defense against cancerous tumor formation.

A study in PNAS describes iOpn is an essential molecular component responsible for maintenance of functional NK cell expansion.

Absence of iOPN results in failure to maintain normal NK cellularity and increased cell death following stimulation by cytokine IL-15.

[99] A study in JCB showed that a specific fragment (SLAYGLR) of the Opn protein can render pDCs more “fit” to protect from melanoma development.

[101][102] Specifically, it plays a central role in the remodeling response to myocardial infarction, and is dramatically upregulated in hypertrophic (HCM) and dilated cardiomyopathy (DCM).

[102] Once abundant, it stimulates a wide range of physiological changes in the myocardium, including angiogenesis, local production of cytokines, differentiation of myofibroblasts, increased deposition of extracellular matrix, and hypertrophy of cardiomyocytes.

[103][104] OPN plays a role in oxidative and nitrosative stress, apoptosis, mitochondrial dysfunction, and excitotoxicity, which are also involved in the pathogenesis of Parkinson's disease.

[105] Evidence is accumulating that suggests that osteopontin plays a number of roles in diseases of skeletal muscle, such as Duchenne muscular dystrophy.

OPN is a vital protein for stromal cell proliferation and differentiation as well as it binds to the receptor αvβ3 to assist with adhesion.